Abstract
Molecular chaperones are a functionally defined set of proteins which assist the structure formation of proteins in vivo. Without certain protective mechanisms, such as binding nascent polypeptide chains by molecular chaperones, cellular protein concentrations would lead to misfolding and aggregation. In the mammalian system, the molecular chaperones Hsp70 and Hsp90 are involved in the folding and maturation of key regulatory proteins, like steroid hormone receptors, transcription factors, and kinases, some of which are involved in cancer progression. Hsp70 and Hsp90 form a multichaperone complex, in which both are connected by a third protein called Hop. The connection of and the interplay between the two chaperone machineries is of crucial importance for cell viability. This review provides a detailed view of the Hsp70 and Hsp90 machineries, their cofactors and their mode of regulation. It summarizes the current knowledge in the field, including the ATP-dependent regulation of the Hsp70/Hsp90 multichaperone cycle and elucidates the complex interplay and their synergistic interaction.
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Abbreviations
- TPR:
-
Tetratricopeptide repeat
- Hsp70:
-
Heat shock protein 70
- yHsp70:
-
Yeast heat shock protein 70
- Hsp90:
-
Heat shock protein 90
- yHsp90:
-
Yeast heat shock protein 90
- hHsp90:
-
Human heat shock protein 90
- SHR:
-
Steroid hormone receptor
- GA:
-
Geldanamycin
- GR:
-
Glucocorticoid receptor
- PR:
-
Progesterone receptor
- ER:
-
Endoplasmic reticulum
- DSG:
-
15-Deoxyspergualin
- GR-LBD:
-
Glucocorticoid receptor ligand binding domain
References
Abbas-Terki T, Picard D (1999) Alpha-complemented beta-galactosidase. An in vivo model substrate for the molecular chaperone heat-shock protein 90 in yeast. Eur J Biochem 266:517–523
Abravaya K, Myers MP, Murphy SP, Morimoto RI (1992) The human heat shock protein hsp70 interacts with HSF, the transcription factor that regulates heat shock gene expression. Genes Dev 6:1153–1164
Adkins B, Hunter T, Sefton BM (1982) The transforming proteins of PRCII virus and Rous sarcoma virus form a complex with the same two cellular phosphoproteins. J Virol 43:448–455
Agarraberes FA, Dice JF (2001) A molecular chaperone complex at the lysosomal membrane is required for protein translocation. J Cell Sci 114:2491–2499
Ali A, Bharadwaj S, O’Carroll R, Ovsenek N (1998) HSP90 interacts with and regulates the activity of heat shock factor 1 in Xenopus oocytes. Mol Cell Biol 18:4949–4960
Aligue R, Akhavan-Niak H, Russell P (1994) A role for Hsp90 in cell cycle control: Wee1 tyrosine kinase activity requires interaction with Hsp90. EMBO J 13:6099–6106
An WG, Schulte TW, Neckers LM (2000) The heat shock protein 90 antagonist geldanamycin alters chaperone association with p210bcr-abl and v-src proteins before their degradation by the proteasome. Cell Growth Differ 11: 355–360
Arbeitman MN, Hogness DS (2000) Molecular chaperones activate the Drosophila ecdysone receptor, an RXR heterodimer. Cell 101:67–77
Ballinger CA, Connell P, Wu Y, Hu Z, Thompson LJ, Yin LY, Patterson C (1999) Identification of CHIP, a novel tetratricopeptide repeat-containing protein that interacts with heat shock proteins and negatively regulates chaperone functions. Mol Cell Biol 19:4535–4545
Ban C, Yang W (1998) Crystal structure and ATPase activity of MutL: implications for DNA repair and mutagenesis. Cell 95:541–552
Banecki B, Zylicz M (1996) Real time kinetics of the DnaK/DnaJ/GrpE molecular chaperone machine action. J Biol Chem 271:6137–6143
Banumathy G, Singh V, Tatu U (2002) Host chaperones are recruited in membrane-bound complexes by Plasmodium falciparum. J Biol Chem 277:3902–3912
Bardwell JC, Craig EA (1988) Ancient heat shock gene is dispensable. J Bacteriol 170:2977–2983
Beckmann RP, Mizzen LE, Welch WJ (1990) Interaction of Hsp 70 with newly synthesized proteins: implications for protein folding and assembly. Science 248:850–854
Bell S, Klein C, Muller L, Hansen S, Buchner J (2002) p53 contains large unstructured regions in its native state. J Mol Biol 322:917–927
Ben Or S (1989) Evidence that 5 S intermediate state in glucocorticoid receptor transformation contains hsp90 in addition to the steroid-binding protein. J Steroid Biochem 33:899–906
Benaroudj N, Batelier G, Triniolles F, Ladjimi MM (1995) Self-association of the molecular chaperone HSC70. Biochemistry 34:15282–15290
Bender AT, Silverstein AM, Demady DR, Kanelakis KC, Noguchi S, Pratt WB, Osawa Y (1999) Neuronal nitric-oxide synthase is regulated by the Hsp90-based chaperone system in vivo. J Biol Chem 274:1472–1478
Bergerat A, de Massy B, Gadelle D, Varoutas PC, Nicolas A, Forterre P (1997) An atypical topoisomerase II from Archaea with implications for meiotic recombination. Nature 386:414–417
Bergmann JE, Lodish HF (1979) A kinetic model of protein synthesis. Application to hemoglobin synthesis and translational control. J Biol Chem 254:11927–11937
Bernstein SL, Russell P, Wong P, Fishelevich R, Smith LE (2001) Heat shock protein 90 in retinal ganglion cells: association with axonally transported proteins. Vis Neurosci 18:429–436
Bijlmakers MJ, Marsh M (2000) Hsp90 is essential for the synthesis and subsequent membrane association, but not the maintenance, of the Src-kinase p56(lck). Mol Biol Cell 11:1585–1595
Bilwes AM, Alex LA, Crane BR, Simon MI (1999) Structure of CheA, a signal-transducing histidine kinase. Cell 96:131–141
Bimston D, Song J, Winchester D, Takayama S, Reed JC, Morimoto RI (1998) BAG-1, a negative regulator of Hsp70 chaperone activity, uncouples nucleotide hydrolysis from substrate release. EMBO J 17:6871–6878
Blagosklonny MV, Toretsky J, Bohen S, Neckers L (1996) Mutant conformation of p53 translated in vitro or in vivo requires functional HSP90. Proc Natl Acad Sci 93:8379–8383
Blond-Elguindi S, Cwirla SE, Dower WJ, Lipshutz RJ, Sprang SR, Sambrook JF, Gething MJ (1993a) Affinity panning of a library of peptides displayed on bacteriophages reveals the binding specificity of BiP. Cell 75: 717–728
Blond-Elguindi S, Fourie AM, Sambrook JF, Gething MJ (1993b) Peptide-dependent stimulation of the ATPase activity of the molecular chaperone BiP is the result of conversion of oligomers to active monomers. J Biol Chem 268:12730–12735
Bogatcheva NV, Ma Y, Urosev D, Gusev NB (1999) Localization of calponin binding sites in the structure of 90-kDa heat shock protein (Hsp90). FEBS Lett 457:369–374
Bohen SP (1998) Genetic and biochemical analysis of p23 and ansamycin antibiotics in the function of Hsp90-dependent signaling proteins. Mol Cell Biol 18:3330–3339
Bolliger L, Deloche O, Glick BS, Georgopoulos C, Jeno P, Kronidou N, Horst M, Morishima N, Schatz G (1994) A mitochondrial homolog of bacterial GrpE interacts with mitochondrial hsp70 and is essential for viability. EMBO J 13:1998–2006
Borkovich KA, Farrelly FW, Finkelstein DB, Taulien J, Lindquist S (1989) hsp82 is an essential protein that is required in higher concentrations for growth of cells at higher temperatures. Mol Cell Biol 9:3919–3930
Bose S, Weikl T, Bugl H, Buchner J (1996) Chaperone function of Hsp90-associated proteins. Science 274: 1715–1717
Brehmer D, Rudiger S, Gassler CS, Klostermeier D, Packschies L, Reinstein J, Mayer MP, Bukau B (2001) Tuning of chaperone activity of Hsp70 proteins by modulation of nucleotide exchange. Nat Struct Biol 8:427–432
Brodsky JL (1999) Selectivity of the molecular chaperone-specific immunosuppressive agent 15-deoxyspergualin: modulation of Hsc70 ATPase activity without compromising DnaJ chaperone interactions. Biochem Pharmacol 57: 877–880
Brugge JS (1986) Interaction of the Rous sarcoma virus protein pp60src with the cellular proteins pp50 and pp90. Curr Top Microbiol Immunol 123:1–22
Brugge JS, Erikson RL (1977) Identification of a transformation-specific antigen induced by an avian sarcoma virus. Nature 269:346–348
Brugge JS, Erikson E, Erikson RL (1981) The specific interaction of the Rous sarcoma virus transforming protein, pp60src, with two cellular proteins. Cell 25:363–372
Bruneau N, Lombardo D, Bendayan M (1998) Participation of GRP94-related protein in secretion of pancreatic bile salt-dependent lipase and in its internalization by the intestinal epithelium. J Cell Sci 111(Pt 17): 2665–2679
Buchberger A, Schroder H, Hesterkamp T, Schonfeld HJ, Bukau B (1996) Substrate shuttling between the DnaK and GroEL systems indicates a chaperone network promoting protein folding. J Mol Biol 261:328–333
Buchner J (1999) Hsp90 & Co.-a holding for folding. Trends Biochem Sci 24:136–141
Bukau B, Horwich AL (1998) The Hsp70 and Hsp60 chaperone machines. Cell 92:351–366
Busconi L, Guan J, Denker BM (2000) Degradation of heterotrimeric Galpha(o) subunits via the proteosome pathway is induced by the hsp90-specific compound geldanamycin. J Biol Chem 275:1565–1569
Carrello A, Ingley E, Minchin RF, Tsai S, Ratajczak T (1999) The common tetratricopeptide repeat acceptor site for steroid receptor-associated immunophilins and hop is located in the dimerization domain of Hsp90. J Biol Chem 274: 2682–2689
Catelli MG, Binart N, Jung-Testas I, Renoir JM, Baulieu EE, Feramisco JR, Welch WJ (1985) The common 90-kd protein component of nontransformed ‘8S’ steroid receptors is a heat-shock protein. EMBO J 4: 3131–3135
Chadli A, Bouhouche I, Sullivan W, Stensgard B, McMahon N, Catelli MG, Toft DO (2000) Dimerization and N-terminal domain proximity underlie the function of the molecular chaperone heat shock protein 90. Proc Natl Acad Sci 97:12524–12529
Chang GC, Liu R, Panniers R, Li GC (1994) Rat fibroblasts transfected with the human 70-kDa heat shock gene exhibit altered translation and eukaryotic initiation factor 2 alpha phosphorylation following heat shock. Int J Hyperthermia 10:325–337
Chang HC, Lindquist S (1994) Conservation of Hsp90 macromolecular complexes in Saccharomyces cerevisiae. J Biol Chem 269:24983–24988
Chang HC, Nathan DF, Lindquist S (1997) In vivo analysis of the Hsp90 cochaperone Sti1 (p60). Mol Cell Biol 17:318–325
Chavany C, Mimnaugh E, Miller P, Bitton R, Nguyen P, Trepel J, Whitesell L, Schnur R, Moyer J, Neckers L (1996) p185erbB2 binds to GRP94 in vivo. Dissociation of the p185erbB2/GRP94 heterocomplex by benzoquinone ansamycins precedes depletion of p185erbB2. J Biol Chem 271:4974–4977
Cheetham ME, Caplan AJ (1998) Structure, function and evolution of DnaJ: conservation and adaptation of chaperone function. Cell Stress Chaperones 3:28–36
Chen CF, Chen Y, Dai K, Chen PL, Riley DJ, Lee WH (1996a) A new member of the hsp90 family of molecular chaperones interacts with the retinoblastoma protein during mitosis and after heat shock. Mol Cell Biol 16: 4691–4699
Chen S, Prapapanich V, Rimerman RA, Honore B, Smith DF (1996b) Interactions of p60, a mediator of progesterone receptor assembly, with heat shock proteins hsp90 and hsp70. Mol Endocrinol 10:682–693
Chen S, Sullivan WP, Toft DO, Smith DF (1998) Differential interactions of p23 and the TPR-containing proteins Hop, Cyp40, FKBP52 and FKBP51 with Hsp90 mutants. Cell Stress Chaperones 3:118–129
Chiosis G, Huezo H, Rosen N, Mimnaugh E, Whitesell L, Neckers L (2003) 17AAG: low target binding affinity and potent cell activity-finding an explanation. Mol Cancer Ther 2:123–129
Clarke PA, Hostein I, Banerji U, Stefano FD, Maloney A, Walton M, Judson I, Workman P (2000) Gene expression profiling of human colon cancer cells following inhibition of signal transduction by 17-allylamino-17-demethoxygeldanamycin, an inhibitor of the hsp90 molecular chaperone. Oncogene 19:4125–4133
Compton JL, McCarthy BJ (1978) Induction of the Drosophila heat shock response in isolated polytene nuclei. Cell 14:191–201
Connell P, Ballinger CA, Jiang J, Wu Y, Thompson LJ, Hohfeld J, Patterson C (2001) The cochaperone CHIP regulates protein triage decisions mediated by heat-shock proteins. Nat Cell Biol 3:93–96
Courtneidge SA, Bishop JM (1982) Transit of pp60v-src to the plasma membrane. Proc Natl Acad Sci 79: 7117–7121
Crevel G, Bates H, Huikeshoven H, Cotterill S (2001) The Drosophila Dpit47 protein is a nuclear Hsp90 cochaperone that interacts with DNA polymerase alpha. J Cell Sci 114:2015–2025
Cutforth T, Rubin GM (1994) Mutations in Hsp83 and cdc37 impair signaling by the sevenless receptor tyrosine kinase in Drosophila. Cell 77:1027–1036
Cyr DM, Douglas MG (1994) Differential regulation of Hsp70 subfamilies by the eukaryotic DnaJ homologue YDJ1. J Biol Chem 269:9798–9804
Cyr DM, Lu X, Douglas MG (1992) Regulation of Hsp70 function by a eukaryotic DnaJ homolog. J Biol Chem 267:20927–20931
Dai K, Kobayashi R, Beach D (1996) Physical interaction of mammalian CDC37 with CDK4. J Biol Chem 271: 22030–22034
Dalman FC, Bresnick EH, Patel PD, Perdew GH, Watson SJ, Jr., Pratt WB (1989) Direct evidence that the glucocorticoid receptor binds to hsp90 at or near the termination of receptor translation in vitro. J Biol Chem 264:19815–19821
Das AK, Cohen PW, Barford D (1998) The structure of the tetratricopeptide repeats of protein phosphatase 5: implications for TPR-mediated protein-protein interactions. EMBO J 17:1192–1199
Davies TH, Ning YM, Sanchez ER (2002) A new first step in activation of steroid receptors: hormone-induced switching of FKBP51 and FKBP52 immunophilins. J Biol Chem 277:4597–4600
Dawson R, Muller L, Dehner A, Klein C, Kessler H, Buchner J (2003) The N-terminal domain of p53 is natively unfolded. J Mol Biol 332:1131–1141
de Carcer G, do Carmo AM, Lallena MJ, Glover DM, Gonzalez C (2001) Requirement of Hsp90 for centrosomal function reflects its regulation of Polo kinase stability. EMBO J 20:2878–2884
Dehner A, Furrer J, Richter K, Schuster I, Buchner J, Kessler H (2003) NMR chemical shift perturbation study of the N-terminal domain of Hsp90 upon binding of ADP, AMP-PNP, geldanamycin, and radicicol. Chembiochem 4: 870–877
Dekker PJ, Pfanner N (1997) Role of mitochondrial GrpE and phosphate in the ATPase cycle of matrix Hsp70. J Mol Biol 270:321–327
Denis M, Cuthill S, Wikstrom AC, Poellinger L, Gustafsson JA (1988) Association of the dioxin receptor with the Mr 90,000 heat shock protein: a structural kinship with the glucocorticoid receptor. Biochem Biophys Res Commun 155: 801–807
Denis M, Gustafsson JA (1989) Translation of glucocorticoid receptor mRNA in vitro yields a nonactivated protein. J Biol Chem 264:6005–6008
Deshaies RJ, Koch BD, Werner-Washburne M, Craig EA, Schekman R (1988) A subfamily of stress proteins facilitates translocation of secretory and mitochondrial precursor polypeptides. Nature 332:800–805
Deuerling E, Patzelt H, Vorderwulbecke S, Rauch T, Kramer G, Schaffitzel E, Mogk A, Schulze-Specking A, Langen H, Bukau B (2003) Trigger factor and DnaK possess overlapping substrate pools and binding specificities. Mol Microbiol 47:1317–1328
Deuerling E, Schulze-Specking A, Tomoyasu T, Mogk A, Bukau B (1999) Trigger factor and DnaK cooperate in folding of newly synthesized proteins. Nature 400:693–696
Dittmar KD, Banach M, Galigniana MD, Pratt WB (1998) The role of DnaJ-like proteins in glucocorticoid receptor hsp90 heterocomplex assembly by the reconstituted hsp90. p60. hsp70 foldosome complex. J Biol Chem 273: 7358–7366
Dittmar KD, Pratt WB (1997) Folding of the glucocorticoid receptor by the reconstituted Hsp90-based chaperone machinery. The initial hsp90. p60. hsp70-dependent step is sufficient for creating the steroid binding conformation. J Biol Chem 272:13047–13054
Donze O, Abbas-Terki T, Picard D (2001) The Hsp90 chaperone complex is both a facilitator and a repressor of the dsRNA-dependent kinase PKR. EMBO J 20:3771–3780
Donze O, Picard D (1999) Hsp90 binds and regulates Gcn2, the ligand-inducible kinase of the alpha subunit of eukaryotic translation initiation factor 2 [corrected]. Mol Cell Biol 19:8422–8432
Duina AA, Marsh JA, Gaber RF (1996) Identification of two CyP-40-like cyclophilins in Saccharomyces cerevisiae, one of which is required for normal growth. Yeast 12:943–952
Dutta R, Inouye M (2000) GHKL, an emergent ATPase/kinase superfamily. Trends Biochem Sci 25:24–28
Erpel T, Courtneidge SA (1995) Src family protein tyrosine kinases and cellular signal transduction pathways. Curr Opin Cell Biol 7:176–182
Evans RM, Hollenberg SM (1988) Cooperative and positional independent trans-activation domains of the human glucocorticoid receptor. Cold Spring Harb Symp Quant Biol 53 Pt 2:813–818
Farrelly FW, Finkelstein DB (1984) Complete sequence of the heat shock-inducible HSP90 gene of Saccharomyces cerevisiae. J Biol Chem 259:5745–5751
Felts SJ, Owen BA, Nguyen P, Trepel J, Donner DB, Toft DO (2000) The hsp90-related protein TRAP1 is a mitochondrial protein with distinct functional properties. J Biol Chem 275:3305–3312
Ferreira LR, Norris K, Smith T, Hebert C, Sauk JJ (1994) Association of Hsp47, Grp78, and Grp94 with procollagen supports the successive or coupled action of molecular chaperones. J Cell Biochem 56:518–526
Fink AL (1997) Molecular chaperones in the life cycle of proteins. Marcel Dekker, New York, pp 123–150
Fisher DL, Mandart E, Doree M (2000) Hsp90 is required for c-Mos activation and biphasic MAP kinase activation in Xenopus oocytes. EMBO J 19:1516–1524
Flaherty KM, DeLuca-Flaherty C, McKay DB (1990) Three-dimensional structure of the ATPase fragment of a 70 K heat-shock cognate protein. Nature 346:623–628
Flaherty KM, McKay DB, Kabsch W, Holmes KC (1991) Similarity of the three-dimensional structures of actin and the ATPase fragment of a 70-kDa heat shock cognate protein. Proc Natl Acad Sci 88:5041–5045
Flanagan CA, Thorner J (1992) Purification and characterization of a soluble phosphatidylinositol 4-kinase from the yeast Saccharomyces cerevisiae. J Biol Chem 267:24117–24125
Fletterick RJ, Bates DJ, Steitz TA (1975) The structure of a yeast hexokinase monomer and its complexes with substrates at 2. 7-A resolution. Proc Natl Acad Sci 72:38–42
Flynn GC, Pohl J, Flocco MT, Rothman JE (1991) Peptide-binding specificity of the molecular chaperone BiP. Nature 353:726–730
Forsythe HL, Jarvis JL, Turner JW, Elmore LW, Holt SE (2001) Stable association of hsp90 and p23, but Not hsp70, with active human telomerase. J Biol Chem 276:15571–15574
Freeman BC, Felts SJ, Toft DO, Yamamoto KR (2000) The p23 molecular chaperones act at a late step in intracellular receptor action to differentially affect ligand efficacies. Genes Dev 14:422–434
Freeman BC, Morimoto RI (1996) The human cytosolic molecular chaperones hsp90, hsp70 (hsc70) and hdj-1 have distinct roles in recognition of a nonnative protein and protein refolding. EMBO J 15:2969–2979
Freeman BC, Toft DO, Morimoto RI (1996) Molecular chaperone machines: chaperone activities of the cyclophilin Cyp-40 and the steroid aporeceptor-associated protein p23. Science 274:1718–1720
Freeman BC, Yamamoto KR (2002) Disassembly of transcriptional regulatory complexes by molecular chaperones. Science 296:2232–2235
Frydman J, Nimmesgern E, Erdjument-Bromage H, Wall JS, Tempst P, Hartl FU (1992) Function in protein folding of TRiC, a cytosolic ring complex containing TCP-1 and structurally related subunits. EMBO J 11:4767–4778
Frydman J, Nimmesgern E, Ohtsuka K, Hartl FU (1994) Folding of nascent polypeptide chains in a high molecular mass assembly with molecular chaperones. Nature 370:111–117
Fujita N, Sato S, Ishida A, Tsuruo T (2002) Involvement of Hsp90 in signaling and stability of 3-phosphoinositide-dependent kinase-1. J Biol Chem 277:10346–10353
Fukazawa H, Li PM, Yamamoto C, Murakami Y, Mizuno S, Uehara Y (1991) Specific inhibition of cytoplasmic protein tyrosine kinases by herbimycin A in vitro. Biochem Pharmacol 42:1661–1671
Gamer J, Bujard H, Bukau B (1992) Physical interaction between heat shock proteins DnaK, DnaJ, and GrpE and the bacterial heat shock transcription factor sigma 32. Cell 69:833–842
Gao B, Emoto Y, Greene L, Eisenberg E (1993) Nucleotide binding properties of bovine brain uncoating ATPase. J Biol Chem 268:8507–8513
Gao B, Greene L, Eisenberg E (1994) Characterization of nucleotide-free uncoating ATPase and its binding to ATP, ADP, and ATP analogues. Biochemistry 33:2048–2054
Garcia-Cardena G, Fan R, Shah V, Sorrentino R, Cirino G, Papapetropoulos A, Sessa WC (1998) Dynamic activation of endothelial nitric oxide synthase by Hsp90. Nature 392:821–824
Garnier C, Lafitte D, Tsvetkov PO, Barbier P, Leclerc-Devin J, Millot JM, Briand C, Makarov AA, Catelli MG, Peyrot V (2002) Binding of ATP to heat shock protein 90: evidence for an ATP-binding site in the C-terminal domain. J Biol Chem 277:12208–12214
Gautschi M, Lilie H, Funfschilling U, Mun A, Ross S, Lithgow T, Rucknagel P, Rospert S (2001) RAC, a stable ribosome-associated complex in yeast formed by the DnaK-DnaJ homologs Ssz1p and zuotin. Proc Natl Acad Sci 98: 3762–3767
Gautschi M, Mun A, Ross S, Rospert S (2002) A functional chaperone triad on the yeast ribosome. Proc Natl Acad Sci 99:4209–4214
Gerber MR, Farrell A, Deshaies RJ, Herskowitz I, Morgan DO (1995) Cdc37 is required for association of the protein kinase Cdc28 with G1 and mitotic cyclins. Proc Natl Acad Sci 92:4651–4655
Giannoukos G, Silverstein AM, Pratt WB, Simons SS, Jr. (1999) The seven amino acids (547–553) of rat glucocorticoid receptor required for steroid and hsp90 binding contain a functionally independent LXXLL motif that is critical for steroid binding. J Biol Chem 274:36527–36536
Gilmore R, Coffey MC, Lee PW (1998) Active participation of Hsp90 in the biogenesis of the trimeric reovirus cell attachment protein sigma1. J Biol Chem 273:15227–15233
Goes FS, Martin J (2001) Hsp90 chaperone complexes are required for the activity and stability of yeast protein kinases Mik1, Wee1 and Swe1. Eur J Biochem 268:2281–2289
Goetz MP, Toft DO, Ames MM, Erlichman C (2003) The Hsp90 chaperone complex as a novel target for cancer therapy. Ann Oncol 14:1169–1176
Gragerov A, Zeng L, Zhao X, Burkholder W, Gottesman ME (1994) Specificity of DnaK-peptide binding. J Mol Biol 235:848–854
Grammatikakis N, Lin JH, Grammatikakis A, Tsichlis PN, Cochran BH (1999) p50(cdc37) acting in concert with Hsp90 is required for Raf-1 function. Mol Cell Biol 19:1661–1672
Grammatikakis N, Vultur A, Ramana CV, Siganou A, Schweinfest CW, Watson DK, Raptis L (2002) The role of Hsp90N, a new member of the Hsp90 family, in signal transduction and neoplastic transformation. J Biol Chem 277: 8312–8320
Greene LE, Zinner R, Naficy S, Eisenberg E (1995) Effect of nucleotide on the binding of peptides to 70-kDa heat shock protein. J Biol Chem 270:2967–2973
Grenert JP, Sullivan WP, Fadden P, Haystead TA, Clark J, Mimnaugh E, Krutzsch H, Ochel HJ, Schulte TW, Sausville E, Neckers LM, Toft DO (1997) The amino-terminal domain of heat shock protein 90 (hsp90) that binds geldanamycin is an ATP/ADP switch domain that regulates hsp90 conformation. J Biol Chem 272:23843–23850
Gusarova V, Caplan AJ, Brodsky JL, Fisher EA (2001) Apoprotein B degradation is promoted by the molecular chaperones hsp90 and hsp70. J Biol Chem 276:24891–24900
Ha JH, Hellman U, Johnson ER, Li L, McKay DB, Sousa MC, Takeda S, Wernstedt C, Wilbanks SM (1997) Destabilization of peptide binding and interdomain communication by an E543 K mutation in the bovine 70-kDa heat shock cognate protein, a molecular chaperone. J Biol Chem 272:27796–27803
Ha JH, Johnson ER, McKay DB, Sousa MC, Takeda S, Wilbanks SM (1999) Structure and mechanism of Hsp70 proteins. In: Molecular chaperones and folding catalysts: regulation, cellular function and mechanisms. Harwood Academic Publishers, pp 573–608
Ha JH, McKay DB (1994) ATPase kinetics of recombinant bovine 70-kDa heat shock cognate protein and its amino-terminal ATPase domain. Biochemistry 33:14625–14635
Ha JH, McKay DB (1995) Kinetics of nucleotide-induced changes in the tryptophan fluorescence of the molecular chaperone Hsc70 and its subfragments suggest the ATP-induced conformational change follows initial ATP binding. Biochemistry 34:11635–11644
Hansen WJ, Lingappa VR, Welch WJ (1994) Complex environment of nascent polypeptide chains. J Biol Chem 269:26610–26613
Harrison CJ, Hayer-Hartl M, Di Liberto M, Hartl F, Kuriyan J (1997) Crystal structure of the nucleotide exchange factor GrpE bound to the ATPase domain of the molecular chaperone DnaK. Science 276:431–435
Hartson SD, Matts RL (1994) Association of Hsp90 with cellular Src-family kinases in a cell-free system correlates with altered kinase structure and function. Biochemistry 33:8912–8920
Hashimoto Y, Shudo K (1991) Cytosolic-nuclear tumor promoter-specific binding protein: association with the 90-kDa heat shock protein and translocation into nuclei by treatment with 12-O-tetradecanoylphorbol 13-acetate. Jpn J Cancer Res 82:665–675
Hendrick JP, Hartl FU (1993) Molecular chaperone functions of heat-shock proteins. Annu Rev Biochem 62: 349–384
Herbertsson H, Kuhme T, Hammarstrom S (1999) The 650-kDa 12(S)-hydroxyeicosatetraenoic acid binding complex: occurrence in human platelets, identification of hsp90 as a constituent, and binding properties of its 50-kDa subunit. Arch Biochem Biophys 367:33–38
Herbst R, Gast K, Seckler R (1998) Folding of firefly (Photinus pyralis) luciferase: aggregation and reactivation of unfolding intermediates. Biochemistry 37:6586–6597
Hernandez MP, Chadli A, Toft DO (2002a) HSP40 binding is the first step in the HSP90 chaperoning pathway for the progesterone receptor. J Biol Chem 277:11873–11881
Hernandez MP, Sullivan WP, Toft DO (2002b) The assembly and intermolecular properties of the hsp70-Hop-hsp90 molecular chaperone complex. J Biol Chem 277:38294–38304
Herrmann JM, Neupert W (2000) Protein transport into mitochondria. Curr Opin Microbiol 3:210–214
Hickey E, Brandon SE, Smale G, Lloyd D, Weber LA (1989) Sequence and regulation of a gene encoding a human 89-kilodalton heat shock protein. Mol Cell Biol 9:2615–2626
Hoff KG, Silberg JJ, Vickery LE (2000) Interaction of the iron-sulfur cluster assembly protein IscU with the Hsc66/Hsc20 molecular chaperone system of Escherichia coli. Proc Natl Acad Sci 97:7790–7795
Hohfeld J, Jentsch S (1997) GrpE-like regulation of the hsc70 chaperone by the anti-apoptotic protein BAG-1. EMBO J 16:6209–6216
Holley SJ, Yamamoto KR (1995) A role for Hsp90 in retinoid receptor signal transduction. Mol Biol Cell 6: 1833–1842
Holt SE, Aisner DL, Baur J, Tesmer VM, Dy M, Ouellette M, Trager JB, Morin GB, Toft DO, Shay JW, Wright WE, White MA (1999) Functional requirement of p23 and Hsp90 in telomerase complexes. Genes Dev 13:817–826
Honore B, Leffers H, Madsen P, Rasmussen HH, Vandekerckhove J, Celis JE (1992) Molecular cloning and expression of a transformation-sensitive human protein containing the TPR motif and sharing identity to the stress-inducible yeast protein STI1. J Biol Chem 267:8485–8491
Hoshino T, Wang J, Devetten MP, Iwata N, Kajigaya S, Wise RJ, Liu JM, Youssoufian H (1998) Molecular chaperone GRP94 binds to the Fanconi anemia group C protein and regulates its intracellular expression. Blood 91: 4379–4386
Howard KJ, Holley SJ, Yamamoto KR, Distelhorst CW (1990) Mapping the HSP90 binding region of the glucocorticoid receptor. J Biol Chem 265:11928–11935
Hu J, Seeger C (1996) Hsp90 is required for the activity of a hepatitis B virus reverse transcriptase. Proc Natl Acad Sci 93:1060–1064
Hu J, Toft DO, Seeger C (1997) Hepadnavirus assembly and reverse transcription require a multi-component chaperone complex which is incorporated into nucleocapsids. EMBO J 16:59–68
Hughes SE, Xiao S, Perera S, Fluno C, Hasselbarth J, Jayasankar V, Singh J, Del Rosario A, Freed BM, Singh TP, Lempert N, Conti DJ, Gruber SA (1996) Local immunosuppression of canine renal allografts with 15-deoxyspergualin. Transplant Proc 28:2054–2055
Hundley H, Eisenman H, Walter W, Evans T, Hotokezaka Y, Wiedmann M, Craig E (2002) The in vivo function of the ribosome-associated Hsp70, Ssz1, does not require its putative peptide-binding domain. Proc Natl Acad Sci 99: 4203–4208
Hunter T (1987a) A tail of two src’s: mutatis mutandis. Cell 49:1–4
Hunter T (1987b) A thousand and one protein kinases. Cell 50:823–829
Hupp TR, Meek DW, Midgley CA, Lane DP (1992) Regulation of the specific DNA binding function of p53. Cell 71:875–886
Hurley JH, Faber HR, Worthylake D, Meadow ND, Roseman S, Pettigrew DW, Remington SJ (1993) Structure of the regulatory complex of Escherichia coli IIIGlc with glycerol kinase. Science 259:673–677
Hutchison KA, Brott BK, De Leon JH, Perdew GH, Jove R, Pratt WB (1992) Reconstitution of the multiprotein complex of pp60src, hsp90, and p50 in a cell-free system. J Biol Chem 267:2902–2908
Hutchison KA, Stancato LF, Owens-Grillo JK, Johnson JL, Krishna P, Toft DO, Pratt WB (1995) The 23-kDa acidic protein in reticulocyte lysate is the weakly bound component of the hsp foldosome that is required for assembly of the glucocorticoid receptor into a functional heterocomplex with hsp90. J Biol Chem 270:18841–18847
Imai J, Yahara I (2000) Role of HSP90 in salt stress tolerance via stabilization and regulation of calcineurin. Mol Cell Biol 20:9262–9270
Inanobe A, Takahashi K, Katada T (1994) Association of the beta gamma subunits of trimeric GTP-binding proteins with 90-kDa heat shock protein, hsp90. J Biochem. (Tokyo) 115:486–492
Itoh T, Matsuda H, Mori H (1999) Phylogenetic analysis of the third hsp70 homolog in Escherichia coli; a novel member of the Hsc66 subfamily and its possible cochaperone. DNA Res 6:299–305
Jaiswal RK, Weissinger E, Kolch W, Landreth GE (1996) Nerve growth factor-mediated activation of the mitogen-activated protein (MAP) kinase cascade involves a signaling complex containing B-Raf and HSP90. J Biol Chem 271:23626–23629
Jakob U, Lilie H, Meyer I, Buchner J (1995) Transient interaction of Hsp90 with early unfolding intermediates of citrate synthase. Implications for heat shock in vivo. J Biol Chem 270:7288–7294
Jerome V, Leger J, Devin J, Baulieu EE, Catelli MG (1991) Growth factors acting via tyrosine kinase receptors induce HSP90 alpha gene expression. Growth Factors 4:317–327
Jiang J, Ballinger CA, Wu Y, Dai Q, Cyr DM, Hohfeld J, Patterson C (2001) CHIP is a U-box-dependent E3 ubiquitin ligase: identification of Hsc70 as a target for ubiquitylation. J Biol Chem 276:42938–42944
Joab I, Radanyi C, Renoir M, Buchou T, Catelli MG, Binart N, Mester J, Baulieu EE (1984) Common nonhormone binding component in nontransformed chick oviduct receptors of four steroid hormones. Nature 308:850–853
Johnson BD, Chadli A, Felts SJ, Bouhouche I, Catelli MG, Toft DO (2000) Hsp90 chaperone activity requires the full-length protein and interaction among its multiple domains. J Biol Chem 275:32499–32507
Johnson BD, Schumacher RJ, Ross ED, Toft DO (1998) Hop modulates Hsp70/Hsp90 interactions in protein folding. J Biol Chem 273:3679–3686
Johnson J, Corbisier R, Stensgard B, Toft D (1996) The involvement of p23, hsp90, and immunophilins in the assembly of progesterone receptor complexes. J Steroid Biochem Mol Biol 56:31–37
Johnson JL, Beito TG, Krco CJ, Toft DO (1994) Characterization of a novel 23-kilodalton protein of unactive progesterone receptor complexes. Mol Cell Biol 14:1956–1963
Johnson JL, Craig EA (2000) A role for the Hsp40 Ydj1 in repression of basal steroid receptor activity in yeast. Mol Cell Biol 20:3027–3036
Johnson JL, Toft DO (1994) A novel chaperone complex for steroid receptors involving heat shock proteins, immunophilins, and p23. J Biol Chem 269:24989–24993
Johnson JL, Toft DO (1995) Binding of p23 and hsp90 during assembly with the progesterone receptor. Mol Endocrinol 9:670–678
Jolly C, Morimoto RI (2000) Role of the heat shock response and molecular chaperones in oncogenesis and cell death. J Natl Cancer Inst 92:1564–1572
Joly GA, Ayres M, Kilbourn RG (1997) Potent inhibition of inducible nitric oxide synthase by geldanamycin, a tyrosine kinase inhibitor, in endothelial, smooth muscle cells, and in rat aorta. FEBS Lett 403:40–44
Kabsch W, Mannherz HG, Suck D, Pai EF, Holmes KC (1990) Atomic structure of the actin: DNase I complex. Nature 347:37–44
Kamal A, Thao L, Sensintaffar J, Zhang L, Boehm MF, Fritz LC, Burrows FJ (2003) A high-affinity conformation of Hsp90 confers tumor selectivity on Hsp90 inhibitors. Nature 425:407–410
Kang J, Kim T, Ko YG, Rho SB, Park SG, Kim MJ, Kwon HJ, Kim S (2000) Heat shock protein 90 mediates protein-protein interactions between human aminoacyl-tRNA synthetases. J Biol Chem 275:31682–31688
Kellermayer MS, Csermely P (1995) ATP induces dissociation of the 90-kDa heat shock protein (hsp90) from F-actin: interference with the binding of heavy meromyosin. Biochem Biophys Res Commun 211:166–174
Kelley WL (1998) The J-domain family and the recruitment of chaperone power. Trends Biochem Sci 23: 222–227
Kim S, Schilke B, Craig EA, Horwich AL (1998) Folding in vivo of a newly translated yeast cytosolic enzyme is mediated by the SSA class of cytosolic yeast Hsp70 proteins. Proc Natl Acad Sci 95:12860–12865
Kimura Y, Rutherford SL, Miyata Y, Yahara I, Freeman BC, Yue L, Morimoto RI, Lindquist S (1997) Cdc37 is a molecular chaperone with specific functions in signal transduction. Genes Dev 11:1775–1785
Klostermeier D, Seidel R, Reinstein J (1998) Functional properties of the molecular chaperone DnaK from Thermus thermophilus. J Mol Biol 279:841–853
Knarr G, Gething MJ, Modrow S, Buchner J (1995) BiP binding sequences in antibodies. J Biol Chem 270: 27589–27594
Knarr G, Kies U, Bell S, Mayer M, Buchner J (2002) Interaction of the chaperone BiP with an antibody domain: implications for the chaperone cycle. J Mol Biol 318:611–620
Knarr G, Modrow S, Todd A, Gething MJ, Buchner J (1999) BiP-binding sequences in HIV gp160. Implications for the binding specificity of bip. J Biol Chem 274:29850–29857
Komori A, Sueoka E, Fujiki H, Ishii M, Kozu T (1999) Association of MTG8 (ETO/CDR), a leukemia-related protein, with serine/threonine protein kinases and heat shock protein HSP90 in human hematopoietic cell lines. Jpn J Cancer Res 90:60–68
Kosano H, Stensgard B, Charlesworth MC, McMahon N, Toft D (1998) The assembly of progesterone receptor-hsp90 complexes using purified proteins. J Biol Chem 273:32973–32979
Koyasu S, Nishida E, Kadowaki T, Matsuzaki F, Iida K, Harada F, Kasuga M, Sakai H, Yahara I (1986) Two mammalian heat shock proteins, HSP90 and HSP100, are actin-binding proteins. Proc Natl Acad Sci 83:8054–8058
Krishna P, Gloor G (2001) The Hsp90 family of proteins in Arabidopsis thaliana. Cell Stress Chaperones 6: 238–246
Kumar R, Grammatikakis N, Chinkers M (2001) Regulation of the atrial natriuretic peptide receptor by heat shock protein 90 complexes. J Biol Chem 276:11371–11375
Kuznetsov G, Chen LB, Nigam SK (1994) Several endoplasmic reticulum stress proteins, including ERp72, interact with thyroglobulin during its maturation. J Biol Chem 269:22990–22995
Lai BT, Chin NW, Stanek AE, Keh W, Lanks KW (1984) Quantitation and intracellular localization of the 85 K heat shock protein by using monoclonal and polyclonal antibodies. Mol Cell Biol 4:2802–2810
Laloraya S, Gambill BD, Craig EA (1994) A role for a eukaryotic GrpE-related protein, Mge1p, in protein translocation. Proc Natl Acad Sci 91:6481–6485
Lamphere L, Fiore F, Xu X, Brizuela L, Keezer S, Sardet C, Draetta GF, Gyuris J (1997) Interaction between Cdc37 and Cdk4 in human cells. Oncogene 14:1999–2004
Landry SJ, Jordan R, McMacken R, Gierasch LM (1992) Different conformations for the same polypeptide bound to chaperones DnaK and GroEL. Nature 355:455–457
Lee P, Rao J, Fliss A, Yang E, Garrett S, Caplan AJ (2002) The Cdc37 protein kinase-binding domain is sufficient for protein kinase activity and cell viability. J Cell Biol 159:1051–1059
Leroux MR (2001) Protein folding and molecular chaperones in archaea. Adv Appl Microbiol 50:219–277
Lewis J, Devin A, Miller A, Lin Y, Rodriguez Y, Neckers L, Liu ZG (2000) Disruption of hsp90 function results in degradation of the death domain kinase, receptor-interacting protein (RIP), and blockage of tumor necrosis factor-induced nuclear factor-kappaB activation. J Biol Chem 275:10519–10526
Liberek K, Marszalek J, Ang D, Georgopoulos C, Zylicz M (1991) Escherichia coli DnaJ and GrpE heat shock proteins jointly stimulate ATPase activity of DnaK. Proc Natl Acad Sci 88:2874–2878
Lipsich LA, Cutt JR, Brugge JS (1982) Association of the transforming proteins of Rous, Fujinami, and Y73 avian sarcoma viruses with the same two cellular proteins. Mol Cell Biol 2:875–880
Little E, Ramakrishnan M, Roy B, Gazit G, Lee AS (1994) The glucose-regulated proteins (GRP78 and GRP94): functions, gene regulation, and applications. Crit Rev Eukaryot Gene Expr 4:1–18
Loo MA, Jensen TJ, Cui L, Hou Y, Chang XB, Riordan JR (1998) Perturbation of Hsp90 interaction with nascent CFTR prevents its maturation and accelerates its degradation by the proteasome. EMBO J 17:6879–6887
Lopez-Buesa P, Pfund C, Craig EA (1998) The biochemical properties of the ATPase activity of a 70-kDa heat shock protein (Hsp70) are governed by the C-terminal domains. Proc Natl Acad Sci 95:15253–15258
Louvion JF, Abbas-Terki T, Picard D (1998) Hsp90 is required for pheromone signaling in yeast. Mol Biol Cell 9:3071–3083
Louvion JF, Warth R, Picard D (1996) Two eukaryote-specific regions of Hsp82 are dispensable for its viability and signal transduction functions in yeast. Proc Natl Acad Sci 93:13937–13942
Lovric J, Bischof O, Moelling K (1994) Cell cycle-dependent association of Gag-Mil and hsp90. FEBS Lett 343:15–21
Lu Z, Cyr DM (1998) Protein folding activity of Hsp70 is modified differentially by the hsp40 cochaperones Sis1 and Ydj1. J Biol Chem 273:27824–27830
Lutz T, Westermann B, Neupert W, Herrmann JM (2001) The mitochondrial proteins Ssq1 and Jac1 are required for the assembly of iron sulfur clusters in mitochondria. J Mol Biol 307:815–825
Macario AJ, Lange M, Ahring BK, De Macario EC (1999) Stress genes and proteins in the archaea. Microbiol Mol Biol Rev 63:923–67
MacLean M, Picard D (2003) Cdc37 goes beyond Hsp90 and kinases. Cell Stress Chaperones 8:114–119
Mahony D, Parry DA, Lees E (1998) Active cdk6 complexes are predominantly nuclear and represent only a minority of the cdk6 in T cells. Oncogene 16:603–611
Marcu MG, Chadli A, Bouhouche I, Catelli M, Neckers LM (2000) The heat shock protein 90 antagonist novobiocin interacts with a previously unrecognized ATP-binding domain in the carboxyl terminus of the chaperone. J Biol Chem 275:37181–37186
Marsh JA, Kalton HM, Gaber RF (1998) Cns1 is an essential protein associated with the hsp90 chaperone complex in Saccharomyces cerevisiae that can restore cyclophilin 40-dependent functions in cpr7Delta cells. Mol Cell Biol 18: 7353–7359
Maruya M, Sameshima M, Nemoto T, Yahara I (1999) Monomer arrangement in HSP90 dimer as determined by decoration with N and C-terminal region specific antibodies. J Mol Biol 285:903–907
Masson-Gadais B, Houle F, Laferriere J, Huot J (2003) Integrin alphavbeta3, requirement for VEGFR2-mediated activation of SAPK2/p38 and for Hsp90-dependent phosphorylation of focal adhesion kinase in endothelial cells activated by VEGF. Cell Stress Chaperones 8:37–52
Matts RL, Hurst R (1989) Evidence for the association of the heme-regulated eIF-2 alpha kinase with the 90-kDa heat shock protein in rabbit reticulocyte lysate in situ. J Biol Chem 264:15542–15547
Mayer M, Reinstein J, Buchner J (2003) Modulation of the ATPase cycle of BiP by peptides and proteins. J Mol Biol 330:137–144
Mayer MP, Brehmer D, Gassler CS, Bukau B (2001) Hsp70 chaperone machines. Adv Protein Chem 59:1–44
Mayer MP, Schroder H, Rudiger S, Paal K, Laufen T, Bukau B (2000) Multistep mechanism of substrate binding determines chaperone activity of Hsp70. Nat Struct Biol 7:586–593
McCarty JS, Buchberger A, Reinstein J, Bukau B (1995) The role of ATP in the functional cycle of the DnaK chaperone system. J Mol Biol 249:126–137
McGuire J, Coumailleau P, Whitelaw ML, Gustafsson JA, Poellinger L (1995) The basic helix-loop-helix/PAS factor Sim is associated with hsp90. Implications for regulation by interaction with partner factors. J Biol Chem 270:31353–31357
McKay DB (1993) Structure and mechanism of 70-kDa heat-shock-related proteins. Adv Protein Chem 44:67–98
McLaughlin SH, Smith HW, Jackson SE (2002) Stimulation of the weak ATPase activity of human hsp90 by a client protein. J Mol Biol 315:787–798
Melnick J, Aviel S, Argon Y (1992) The endoplasmic reticulum stress protein GRP94, in addition to BiP, associates with unassembled immunoglobulin chains. J Biol Chem 267:21303–21306
Meyer P, Prodromou C, Hu B, Vaughan C, Roe SM, Panaretou B, Piper PW, Pearl LH (2003) Structural and functional analysis of the middle segment of hsp90: implications for ATP hydrolysis and client protein and cochaperone interactions. Mol Cell 11:647–658
Milani V, Noessner E, Ghose S, Kuppner M, Ahrens B, Scharner A, Gastpar R, Issels RD (2002) Heat shock protein 70: role in antigen presentation and immune stimulation. Int J Hyperthermia 18:563–575
Miller P, Schnur RC, Barbacci E, Moyer MP, Moyer JD (1994) Binding of benzoquinoid ansamycins to p100 correlates with their ability to deplete the erbB2 gene product p185. Biochem Biophys Res Commun 201:1313–1319
Mimnaugh EG, Chavany C, Neckers L (1996) Polyubiquitination and proteasomal degradation of the p185c-erbB-2 receptor protein-tyrosine kinase induced by geldanamycin. J Biol Chem 271:22796–22801
Mimnaugh EG, Worland PJ, Whitesell L, Neckers LM (1995) Possible role for serine/threonine phosphorylation in the regulation of the heteroprotein complex between the hsp90 stress protein and the pp60vsrc tyrosine kinase. J Biol Chem 270:28654–28659
Minami M, Nakamura M, Emori Y, Minami Y (2001) Both the N-and C-terminal chaperone sites of Hsp90 participate in protein refolding. Eur J Biochem 268:2520–2524
Minet E, Mottet D, Michel G, Roland I, Raes M, Remacle J, Michiels C (1999) Hypoxia-induced activation of HIF-1: role of HIF-1alpha-Hsp90 interaction. FEBS Lett 460:251–256
Minton AP, Colclasure GC, Parker JC (1992) Model for the role of macromolecular crowding in regulation of cellular volume. Proc Natl Acad Sci 89:10504–10506
Miyata Y, Ikawa Y, Shibuya M, Nishida E (2001) Specific association of a set of molecular chaperones including HSP90 and Cdc37 with MOK, a member of the mitogen-activated protein kinase superfamily. J Biol Chem 276: 21841–21848
Miyata Y, Yahara I (1992) The 90-kDa heat shock protein, HSP90, binds and protects casein kinase II from self-aggregation and enhances its kinase activity. J Biol Chem 267:7042–7047
Miyata Y, Yahara I (2000) p53-independent association between SV40 large T antigen and the major cytosolic heat shock protein, HSP90. Oncogene 19:1477–1484
Mizuno K, Shirogane T, Shinohara A, Iwamatsu A, Hibi M, Hirano T (2001) Regulation of Pim-1 by Hsp90. Biochem Biophys Res Commun 281:663–669
Mogk A, Tomoyasu T, Goloubinoff P, Rudiger S, Roder D, Langen H, Bukau B (1999) Identification of thermolabile Escherichia coli proteins: prevention and reversion of aggregation by DnaK and ClpB. EMBO J 18:6934–6949
Morano KA, Thiele DJ (1999) The Sch9 protein kinase regulates Hsp90 chaperone complex signal transduction activity in vivo. EMBO J 18:5953–5962
Morishima Y, Kanelakis KC, Silverstein AM, Dittmar KD, Estrada L, Pratt WB (2000a) The Hsp organizer protein hop enhances the rate of but is not essential for glucocorticoid receptor folding by the multiprotein Hsp90-based chaperone system. J Biol Chem 275:6894–6900
Morishima Y, Murphy PJ, Li DP, Sanchez ER, Pratt WB (2000b) Stepwise assembly of a glucocorticoid receptor hsp90 heterocomplex resolves two sequential ATP-dependent events involving first hsp70 and then hsp90 in opening of the steroid binding pocket. J Biol Chem 275:18054–18060
Multhoff G (2002) Activation of natural killer cells by heat shock protein 70. Int J Hyperthermia 18: 576–585
Munoz MJ, Jimenez J (1999) Genetic interactions between Hsp90 and the Cdc2 mitotic machinery in the fission yeast Schizosaccharomyces pombe. Mol Gen Genet 261:242–250
Muresan Z, Arvan P (1997) Thyroglobulin transport along the secretory pathway. Investigation of the role of molecular chaperone, GRP94, in protein export from the endoplasmic reticulum. J Biol Chem 272:26095–26102
Murphy SM, Bergman M, Morgan DO (1993) Suppression of c-Src activity by C-terminal Src kinase involves the c-Src SH2 and SH3 domains: analysis with Saccharomyces cerevisiae. Mol Cell Biol 13:5290–5300
Murzin AG (1995) A ribosomal protein module in EF-G and DNA gyrase. Nat Struct Biol 2:25–26
Nadeau K, Sullivan MA, Bradley M, Engman DM, Walsh CT (1992) 83-kilodalton heat shock proteins of trypanosomes are potent peptide-stimulated ATPases. Protein Sci 1:970–979
Nadler SG, Tepper MA, Schacter B, Mazzucco CE (1992) Interaction of the immunosuppressant deoxyspergualin with a member of the Hsp70 family of heat shock proteins. Science 258:484–486
Nair SC, Toran EJ, Rimerman RA, Hjermstad S, Smithgall TE, Smith DF (1996) A pathway of multi-chaperone interactions common to diverse regulatory proteins: estrogen receptor, Fes tyrosine kinase, heat shock transcription factor Hsf1, and the aryl hydrocarbon receptor. Cell Stress Chaperones 1:237–250
Nakai M, Kato Y, Ikeda E, Toh-e A, Endo T (1994) Yge1p, a eukaryotic Grp-E homolog, is localized in the mitochondrial matrix and interacts with mitochondrial Hsp70. Biochem Biophys Res Commun 200:435–442
Nakamura T, Hinagata J, Tanaka T, Imanishi T, Wada Y, Kodama T, Doi T (2002) HSP90, HSP70, and GAPDH directly interact with the cytoplasmic domain of macrophage scavenger receptors. Biochem Biophys Res Commun 290: 858–864
Nathan DF, Lindquist S (1995) Mutational analysis of Hsp90 function: interactions with a steroid receptor and a protein kinase. Mol Cell Biol 15:3917–3925
Nathan DF, Vos MH, Lindquist S (1997) In vivo functions of the Saccharomyces cerevisiae Hsp90 chaperone. Proc Natl Acad Sci 94:12949–12956
Navarro D, Qadri I, Pereira L (1991) A mutation in the ectodomain of herpes simplex virus 1 glycoprotein B causes defective processing and retention in the endoplasmic reticulum. Virology 184:253–264
Nelson RJ, Ziegelhoffer T, Nicolet C, Werner-Washburne M, Craig EA (1992) The translation machinery and 70 kd heat shock protein cooperate in protein synthesis. Cell 71:97–105
Nemoto T, Matsusaka T, Ota M, Takagi T, Collinge DB, Walther-Larsen H (1996) Dimerization characteristics of the 94-kDa glucose-regulated protein. J Biochem. (Tokyo) 120:249–256
Nicchitta CV (1998) Biochemical, cell biological and immunological issues surrounding the endoplasmic reticulum chaperone GRP94/gp96. Curr Opin Immunol 10:103–109
Nicolet CM, Craig EA (1989) Isolation and characterization of STI1, a stress-inducible gene from Saccharomyces cerevisiae. Mol Cell Biol 9:3638–3646
Nimmesgern E, Hartl FU (1993) ATP-dependent protein refolding activity in reticulocyte lysate. Evidence for the participation of different chaperone components. FEBS Lett 331:25–30
Nollen EA, Brunsting JF, Song J, Kampinga HH, Morimoto RI (2000) Bag1 functions in vivo as a negative regulator of Hsp70 chaperone activity. Mol Cell Biol 20:1083–1088
Obermann WM, Sondermann H, Russo AA, Pavletich NP, Hartl FU (1998) In vivo function of Hsp90 is dependent on ATP binding and ATP hydrolysis. J Cell Biol 143:901–910
O’Brien MC, Flaherty KM, McKay DB (1996) Lysine 71 of the chaperone protein Hsc70 Is essential for ATP hydrolysis. J Biol Chem 271:15874–15878
O’Brien MC, McKay DB (1993) Threonine 204 of the chaperone protein Hsc70 influences the structure of the active site, but is not essential for ATP hydrolysis. J Biol Chem 268:24323–24329
O’Brien MC, McKay DB (1995) How potassium affects the activity of the molecular chaperone Hsc70. I. Potassium is required for optimal ATPase activity. J Biol Chem 270:2247–2250
Ochel HJ, Eichhorn K, Gademann G (2001) Geldanamycin: the prototype of a class of antitumor drugs targeting the heat shock protein 90 family of molecular chaperones. Cell Stress Chaperones 6:105–112
Odunuga OO, Hornby JA, Bies C, Zimmermann R, Pugh DJ, Blatch GL (2003) Tetratricopeptide repeat motif-mediated Hsc70-mSTI1 interaction. Molecular characterization of the critical contacts for successful binding and specificity. J Biol Chem 278:6896–6904
O’Keeffe B, Fong Y, Chen D, Zhou S, Zhou Q (2000) Requirement for a kinase-specific chaperone pathway in the production of a Cdk9/cyclin T1 heterodimer responsible for P-TEFb-mediated tat stimulation of HIV-1 transcription. J Biol Chem 275:279–287
Oppermann H, Levinson W, Bishop JM (1981) A cellular protein that associates with the transforming protein of Rous sarcoma virus is also a heat-shock protein. Proc Natl Acad Sci 78:1067–1071
Osipiuk J, Walsh MA, Freeman BC, Morimoto RI, Joachimiak A (1999) Structure of a new crystal form of human Hsp70 ATPase domain. Acta Crystallogr D Biol Crystallogr 55:1105–1107
Owen BA, Sullivan WP, Felts SJ, Toft DO (2002) Regulation of heat shock protein 90 ATPase activity by sequences in the carboxyl terminus. J Biol Chem 277:7086–7091
Owens-Grillo JK, Czar MJ, Hutchison KA, Hoffmann K, Perdew GH, Pratt WB (1996a) A model of protein targeting mediated by immunophilins and other proteins that bind to hsp90 via tetratricopeptide repeat domains. J Biol Chem 271:13468–13475
Owens-Grillo JK, Stancato LF, Hoffmann K, Pratt WB, Krishna P (1996b) Binding of immunophilins to the 90-kDa heat shock protein (hsp90) via a tetratricopeptide repeat domain is a conserved protein interaction in plants. Biochemistry 35:15249–15255
Packschies L, Theyssen H, Buchberger A, Bukau B, Goody RS, Reinstein J (1997) GrpE accelerates nucleotide exchange of the molecular chaperone DnaK with an associative displacement mechanism. Biochemistry 36: 3417–3422
Pai KS, Mahajan VB, Lau A, Cunningham DD (2001) Thrombin receptor signaling to cytoskeleton requires Hsp90. J Biol Chem 276:32642–32647
Palleros DR, Reid KL, Shi L, Welch WJ, Fink AL (1993) ATP-induced protein-Hsp70 complex dissociation requires K+ but not ATP hydrolysis. Nature 365:664–666
Palmquist K, Riis B, Nilsson A, Nygard O (1994) Interaction of the calcium and calmodulin regulated eEF-2 kinase with heat shock protein 90. FEBS Lett 349:239–242
Panaretou B, Prodromou C, Roe SM, O’Brien R, Ladbury JE, Piper PW, Pearl LH (1998) ATP binding and hydrolysis are essential to the function of the Hsp90 molecular chaperone in vivo. EMBO J 17:4829–4836
Panaretou B, Siligardi G, Meyer P, Maloney A, Sullivan JK, Singh S, Millson SH, Clarke PA, Naaby-Hansen S, Stein R, Cramer R, Mollapour M, Workman P, Piper PW, Pearl LH, Prodromou C (2002) Activation of the ATPase activity of hsp90 by the stress-regulated cochaperone aha1. Mol Cell 10:1307–1318
Pearl LH, Prodromou C (2000) Structure and in vivo function of Hsp90. Curr Opin Struct Biol 10:46–51
Peng Y, Chen L, Li C, Lu W, Chen J (2001) Inhibition of MDM 2 by hsp90 contributes to mutant p53 stabilization. J Biol Chem 276:40583–40590
Perdew GH (1988) Association of the Ah receptor with the 90-kDa heat shock protein. J Biol Chem 263: 13802–13805
Perdew GH, Hord N, Hollenback CE, Welsh MJ (1993) Localization and characterization of the 86-and 84-kDa heat shock proteins in Hepa 1c1c7 cells. Exp Cell Res 209:350–356
Perdew GH, Whitelaw ML (1991) Evidence that the 90-kDa heat shock protein (HSP90) exists in cytosol in heteromeric complexes containing HSP70 and three other proteins with Mr of 63,000, 56,000, and 50,000. J Biol Chem 266: 6708–6713
Pfanner N (2000) Protein sorting: recognizing mitochondrial presequences. Curr Biol 10:R412–R415
Pfund C, Lopez-Hoyo N, Ziegelhoffer T, Schilke BA, Lopez-Buesa P, Walter WA, Wiedmann M, Craig EA (1998) The molecular chaperone Ssb from Saccharomyces cerevisiae is a component of the ribosome-nascent chain complex. EMBO J 17:3981–3989
Picard D (2002) Heat-shock protein 90, a chaperone for folding and regulation. Cell Mol Life Sci 59: 1640–1648
Pierpaoli EV, Gisler SM, Christen P (1998) Sequence-specific rates of interaction of target peptides with the molecular chaperones DnaK and DnaJ. Biochemistry 37:16741–16748
Piper PW (2001) The Hsp90 chaperone as a promising drug target. Curr Opin Investig Drugs 2:1606–1610
Pratt WB, Scherrer LC, Hutchison KA, Dalman FC (1992) A model of glucocorticoid receptor unfolding and stabilization by a heat shock protein complex. J Steroid Biochem Mol Biol 41:223–229
Pratt WB, Toft DO (1997) Steroid receptor interactions with heat shock protein and immunophilin chaperones. Endocr Rev 18:306–360
Pratt WB, Toft DO (2003) Regulation of signaling protein function and trafficking by the hsp90/hsp70-based chaperone machinery. Exp Biol Med. (Maywood.) 228:111–133
Privalsky ML (1991) A subpopulation of the v-erb A oncogene protein, a derivative of a thyroid hormone receptor, associates with heat shock protein 90. J Biol Chem 266:1456–1462
Prodromou C, Panaretou B, Chohan S, Siligardi G, O’Brien R, Ladbury JE, Roe SM, Piper PW, Pearl LH (2000) The ATPase cycle of Hsp90 drives a molecular “clamp” via transient dimerization of the N-terminal domains. EMBO J 19:4383–4392
Prodromou C, Roe SM, O’Brien R, Ladbury JE, Piper PW, Pearl LH (1997a) Identification and structural characterization of the ATP/ADP-binding site in the Hsp90 molecular chaperone. Cell 90:65–75
Prodromou C, Roe SM, Piper PW, Pearl LH (1997b) A molecular clamp in the crystal structure of the Nterminal domain of the yeast Hsp90 chaperone. Nat Struct Biol 4:477–482
Prodromou C, Siligardi G, O’Brien R, Woolfson DN, Regan L, Panaretou B, Ladbury JE, Piper PW, Pearl LH (1999) Regulation of Hsp90 ATPase activity by tetratricopeptide repeat (TPR)-domain cochaperones. EMBO J 18: 754–762
Queitsch C, Sangster TA, Lindquist S (2002) Hsp90 as a capacitor of phenotypic variation. Nature 417: 618–624
Rafestin-Oblin ME, Couette B, Radanyi C, Lombes M, Baulieu EE (1989) Mineralocorticosteroid receptor of the chick intestine. Oligomeric structure and transformation. J Biol Chem 264:9304–9309
Ramsey AJ, Russell LC, Whitt SR, Chinkers M (2000) Overlapping sites of tetratricopeptide repeat protein binding and chaperone activity in heat shock protein 90. J Biol Chem 275:17857–17862
Rebbe NF, Ware J, Bertina RM, Modrich P, Stafford DW (1987) Nucleotide sequence of a cDNA for a member of the human 90-kDa heat-shock protein family. Gene 53:235–245
Richter K, Buchner J (2001) Hsp90: chaperoning signal transduction. J Cell Physiol 188:281–290
Richter K, Muschler P, Hainzl O, Buchner J (2001) Coordinated ATP hydrolysis by the Hsp90 dimer. J Biol Chem 276:33689–33696
Richter K, Muschler P, Hainzl O, Reinstein J, Buchner J (2003) Sti1 is a noncompetitive inhibitor of the Hsp90 ATPase. Binding prevents the N-terminal dimerization reaction during the atpase cycle. J Biol Chem 278: 10328–10333
Richter K, Reinstein J, Buchner J (2002) N-terminal residues regulate the catalytic efficiency of the Hsp90 ATPase cycle. J Biol Chem 277:44905–44910
Riggs DL, Roberts PJ, Chirillo SC, Cheung-Flynn J, Prapapanich V, Ratajczak T, Gaber R, Picard D, Smith DF (2003) The Hsp90-binding peptidylprolyl isomerase FKBP52 potentiates glucocorticoid signaling in vivo. EMBO J 22: 1158–1167
Roe SM, Prodromou C, O’Brien R, Ladbury JE, Piper PW, Pearl LH (1999) Structural basis for inhibition of the Hsp90 molecular chaperone by the antitumor antibiotics radicicol and geldanamycin. J Med Chem 42:260–266
Rose DW, Wettenhall RE, Kudlicki W, Kramer G, Hardesty B (1987) The 90-kilodalton peptide of the heme-regulated eIF-2 alpha kinase has sequence similarity with the 90-kilodalton heat shock protein. Biochemistry 26: 6583–6587
Rudiger S, Buchberger A, Bukau B (1997a) Interaction of Hsp70 chaperones with substrates. Nat Struct Biol 4:342–349
Rudiger S, Germeroth L, Schneider-Mergener J, Bukau B (1997b) Substrate specificity of the DnaK chaperone determined by screening cellulose-bound peptide libraries. EMBO J 16:1501–1507
Rudiger S, Mayer MP, Schneider-Mergener J, Bukau B (2000) Modulation of substrate specificity of the DnaK chaperone by alteration of a hydrophobic arch. J Mol Biol 304:245–251
Rudiger S, Schneider-Mergener J, Bukau B (2001) Its substrate specificity characterizes the DnaJ cochaperone as a scanning factor for the DnaK chaperone. EMBO J 20:1042–1050
Rutherford SL, Lindquist S (1998) Hsp90 as a capacitor for morphological evolution. Nature 396:336–342
Sabbah M, Redeuilh G, Baulieu EE (1989) Subunit composition of the estrogen receptor. Involvement of the hormone-binding domain in the dimeric state. J Biol Chem 264:2397–2400
Sakagami M, Morrison P, Welch WJ (1999) Benzoquinoid ansamycins (herbimycin A and geldanamycin) interfere with the maturation of growth factor receptor tyrosine kinases. Cell Stress Chaperones 4:19–28
Saleh A, Srinivasula SM, Balkir L, Robbins PD, Alnemri ES (2000) Negative regulation of the Apaf-1 apoptosome by Hsp70. Nat Cell Biol 2:476–483
Sanchez ER, Meshinchi S, Schlesinger MJ, Pratt WB (1987) Demonstration that the 90-kilodalton heat shock protein is bound to the glucocorticoid receptor in its 9S nondeoxynucleic acid binding form. Mol Endocrinol 1:908–912
Sanchez ER, Redmond T, Scherrer LC, Bresnick EH, Welsh MJ, Pratt WB (1988) Evidence that the 90-kilodalton heat shock protein is associated with tubulin-containing complexes in L cell cytosol and in intact PtK cells. Mol Endocrinol 2:756–760
Sato S, Fujita N, Tsuruo T (2000) Modulation of Akt kinase activity by binding to Hsp90. Proc Natl Acad Sci 97:10832–10837
Schaiff WT, Hruska KA, Jr., McCourt DW, Green M, Schwartz BD (1992) HLA-DR associates with specific stress proteins and is retained in the endoplasmic reticulum in invariant chain negative cells. J Exp Med 176: 657–666
Schatz G, Dobberstein B (1996) Common principles of protein translocation across membranes. Science 271: 1519–1526
Scheibel T, Neuhofen S, Weikl T, Mayr C, Reinstein J, Vogel PD, Buchner J (1997) ATP-binding properties of human Hsp90. J Biol Chem 272:18608–18613
Scheibel T, Siegmund HI, Jaenicke R, Ganz P, Lilie H, Buchner J (1999) The charged region of Hsp90 modulates the function of the N-terminal domain. Proc Natl Acad Sci 96:1297–1302
Scheibel T, Weikl T, Buchner J (1998) Two chaperone sites in Hsp90 differing in substrate specificity and ATP dependence. Proc Natl Acad Sci 95:1495–1499
Scherrer LC, Dalman FC, Massa E, Meshinchi S, Pratt WB (1990) Structural and functional reconstitution of the glucocorticoid receptor-hsp90 complex. J Biol Chem 265:21397–21400
Scheufler C, Brinker A, Bourenkov G, Pegoraro S, Moroder L, Bartunik H, Hartl FU, Moarefi I (2000) Structure of TPR domain-peptide complexes: critical elements in the assembly of the Hsp70-Hsp90 multichaperone machine. Cell 101:199–210
Schiene-Fischer C, Habazettl J, Schmid FX, Fischer G (2002) The hsp70 chaperone DnaK is a secondary amide peptide bond cis-trans isomerase. Nat Struct Biol 9:419–424
Schmid D, Baici A, Gehring H, Christen P (1994) Kinetics of molecular chaperone action. Science 263: 971–973
Schmid SL, Braell WA, Rothman JE (1985) ATP catalyzes the sequestration of clathrin during enzymatic uncoating. J Biol Chem 260:10057–10062
Schmid SL, Rothman JE (1985) Two classes of binding sites for uncoating protein in clathrin triskelions. J Biol Chem 260:10050–10056
Schneider C, Sepp-Lorenzino L, Nimmesgern E, Ouerfelli O, Danishefsky S, Rosen N, Hartl FU (1996) Pharmacologic shifting of a balance between protein refolding and degradation mediated by Hsp90. Proc Natl Acad Sci 93: 14536–14541
Schnur RC, Corman ML, Gallaschun RJ, Cooper BA, Dee MF, Doty JL, Muzzi ML, DiOrio CI, Barbacci EG, Miller PE (1995a) erbB-2 oncogene inhibition by geldanamycin derivatives: synthesis, mechanism of action, and structure-activity relationships. J Med Chem 38:3813–3820
Schnur RC, Corman ML, Gallaschun RJ, Cooper BA, Dee MF, Doty JL, Muzzi ML, Moyer JD, DiOrio CI, Barbacci EG (1995b) Inhibition of the oncogene product p185erbB-2 in vitro and in vivo by geldanamycin and dihydrogeldanamycin derivatives. J Med Chem 38:3806–3812
Scholz G, Hartson SD, Cartledge K, Hall N, Shao J, Dunn AR, Matts RL (2000) p50(Cdc37) can buffer the temperature-sensitive properties of a mutant of Hck. Mol Cell Biol 20:6984–6995
Schonfeld HJ, Schmidt D, Schroder H, Bukau B (1995) The DnaK chaperone system of Escherichia coli: quaternary structures and interactions of the DnaK and GrpE components. J Biol Chem 270:2183–2189
Schroder H, Langer T, Hartl FU, Bukau B (1993) DnaK, DnaJ and GrpE form a cellular chaperone machinery capable of repairing heat-induced protein damage. EMBO J 12:4137–4144
Schuh S, Yonemoto W, Brugge J, Bauer VJ, Riehl RM, Sullivan WP, Toft DO (1985) A 90,000-dalton binding protein common to both steroid receptors and the Rous sarcoma virus transforming protein, pp60v-src. J Biol Chem 260: 14292–14296
Schulte TW, Blagosklonny MV, Ingui C, Neckers L (1995) Disruption of the Raf-1-Hsp90 molecular complex results in destabilization of Raf-1 and loss of Raf-1-Ras association. J Biol Chem 270:24585–24588
Schumacher RJ, Hurst R, Sullivan WP, McMahon NJ, Toft DO, Matts RL (1994) ATP-dependent chaperoning activity of reticulocyte lysate. J Biol Chem 269:9493–9499
Schwimmer C, Masison DC (2002) Antagonistic interactions between yeast [PSI(+)] and [URE3] prions and curing of [URE3] by Hsp70 protein chaperone Ssa1p but not by Ssa2p. Mol Cell Biol 22:3590–3598
Sepehrnia B, Paz IB, Dasgupta G, Momand J (1996) Heat shock protein 84 forms a complex with mutant p53 protein predominantly within a cytoplasmic compartment of the cell. J Biol Chem 271:15084–15090
Shao J, Grammatikakis N, Scroggins BT, Uma S, Huang W, Chen JJ, Hartson SD, Matts RL (2001) Hsp90 regulates p50(cdc37) function during the biogenesis of the active conformation of the heme-regulated eIF2 alpha kinase. J Biol Chem 276:206–214
Shiu RP, Pouyssegur J, Pastan I (1977) Glucose depletion accounts for the induction of two transformation-sensitive membrane proteins in Rous sarcoma virus-transformed chick embryo fibroblasts. Proc Natl Acad Sci 74: 3840–3844
Siegers K, Waldmann T, Leroux MR, Grein K, Shevchenko A, Schiebel E, Hartl FU (1999) Compartmentation of protein folding in vivo: sequestration of nonnative polypeptide by the chaperonin-GimC system. EMBO J 18:75–84
Sikorski RS, Boguski MS, Goebl M, Hieter P (1990) A repeating amino acid motif in CDC23 defines a family of proteins and a new relationship among genes required for mitosis and RNA synthesis. Cell 60:307–317
Siligardi G, Panaretou B, Meyer P, Singh S, Woolfson DN, Piper PW, Pearl LH, Prodromou C (2002) Regulation of Hsp90 ATPase activity by the cochaperone Cdc37p/p50cdc37. J Biol Chem 277:20151–20159
Silverstein AM, Grammatikakis N, Cochran BH, Chinkers M, Pratt WB (1998) p50(cdc37) binds directly to the catalytic domain of Raf as well as to a site on hsp90 that is topologically adjacent to the tetratricopeptide repeat binding site. J Biol Chem 273:20090–20095
Smith DF (1993) Dynamics of heat shock protein 90-progesterone receptor binding and the disactivation loop model for steroid receptor complexes. Mol Endocrinol 7:1418–1429
Smith DF, Faber LE, Toft DO (1990) Purification of unactivated progesterone receptor and identification of novel receptor-associated proteins. J Biol Chem 265:3996–4003
Smith DF, Stensgard BA, Welch WJ, Toft DO (1992) Assembly of progesterone receptor with heat shock proteins and receptor activation are ATP mediated events. J Biol Chem 267:1350–1356
Smith DF, Sullivan WP, Marion TN, Zaitsu K, Madden B, McCormick DJ, Toft DO (1993) Identification of a 60-kilodalton stress-related protein, p60, which interacts with hsp90 and hsp70. Mol Cell Biol 13:869–876
Smith DF, Toft DO (1993) Steroid receptors and their associated proteins. Mol Endocrinol 7:4–11
Smith DF, Whitesell L, Nair SC, Chen S, Prapapanich V, Rimerman RA (1995) Progesterone receptor structure and function altered by geldanamycin, an hsp90-binding agent. Mol Cell Biol 15:6804–6812
Sondermann H, Ho AK, Listenberger LL, Siegers K, Moarefi I, Wente SR, Hartl FU, Young JC (2002) Prediction of novel Bag-1 homologs based on structure/function analysis identifies Snl1p as an Hsp70 cochaperone in Saccharomyces cerevisiae. J Biol Chem 277:33220–33227
Song HY, Dunbar JD, Zhang YX, Guo D, Donner DB (1995) Identification of a protein with homology to hsp90 that binds the type 1 tumor necrosis factor receptor. J Biol Chem 270:3574–3581
Song J, Takeda M, Morimoto RI (2001) Bag1-Hsp70 mediates a physiological stress signaling pathway that regulates Raf-1/ERK and cell growth. Nat Cell Biol 3:276–282
Sorger PK, Pelham HR (1987) The glucose-regulated protein grp94 is related to heat shock protein hsp90. J Mol Biol 194:341–344
Soti C, Racz A, Csermely P (2002) A Nucleotide-dependent molecular switch controls ATP binding at the C-terminal domain of Hsp90. N-terminal nucleotide binding unmasks a C-terminal binding pocket. J Biol Chem 277: 7066–7075
Spence J, Cegielska A, Georgopoulos C (1990) Role of Escherichia coli heat shock proteins DnaK and HtpG (C62. 5) in response to nutritional deprivation. J Bacteriol 172:7157–7166
Spence J, Georgopoulos C (1989) Purification and properties of the Escherichia coli heat shock protein, HtpG. J Biol Chem 264:4398–4403
Sreedhar AS, Mihaly K, Pato B, Schnaider T, Stetak A, Kis-Petik K, Fidy J, Simonics T, Maraz A, Csermely P (2003) Hsp90 inhibition accelerates cell lysis. Anti-Hsp90 ribozyme reveals a complex mechanism of Hsp90 inhibitors involving both superoxide-and Hsp90-dependent events. J Biol Chem 278:35231–35240
Stancato LF, Chow YH, Hutchison KA, Perdew GH, Jove R, Pratt WB (1993) Raf exists in a native heterocomplex with hsp90 and p50 that can be reconstituted in a cell-free system. J Biol Chem 268:21711–21716
Stancato LF, Silverstein AM, Owens-Grillo JK, Chow YH, Jove R, Pratt WB (1997) The hsp90-binding antibiotic geldanamycin decreases Raf levels and epidermal growth factor signaling without disrupting formation of signaling complexes or reducing the specific enzymatic activity of Raf kinase. J Biol Chem 272:4013–4020
Stebbins CE, Russo AA, Schneider C, Rosen N, Hartl FU, Pavletich NP (1997) Crystal structure of an Hsp90-geldanamycin complex: targeting of a protein chaperone by an antitumor agent. Cell 89:239–250
Stepanova L, Leng X, Parker SB, Harper JW (1996) Mammalian p50Cdc37 is a protein kinase-targeting subunit of Hsp90 that binds and stabilizes Cdk4. Genes Dev 10:1491–1502
Stewart S, Sundaram M, Zhang Y, Lee J, Han M, Guan KL (1999) Kinase suppressor of Ras forms a multiprotein signaling complex and modulates MEK localization. Mol Cell Biol 19:5523–5534
Sullivan WP, Owen BA, Toft DO (2002) The influence of ATP and p23 on the conformation of hsp90. J Biol Chem 277:45942–45948
Szabo A, Langer T, Schroder H, Flanagan J, Bukau B, Hartl FU (1994) The ATP hydrolysis-dependent reaction cycle of the Escherichia coli Hsp70 system DnaK, DnaJ, and GrpE. Proc Natl Acad Sci 91:10345–10349
Szyszka R, Kramer G, Hardesty B (1989) The phosphorylation state of the reticulocyte 90-kDa heat shock protein affects its ability to increase phosphorylation of peptide initiation factor 2 alpha subunit by the heme-sensitive kinase. Biochemistry 28:1435–1438
Takata Y, Imamura T, Iwata M, Usui I, Haruta T, Nandachi N, Ishiki M, Sasaoka T, Kobayashi M (1997) Functional importance of heat shock protein 90 associated with insulin receptor on insulin-stimulated mitogenesis. Biochem Biophys Res Commun 237:345–347
Taniguchi M, Uehara Y, Matsuyama M, Takahashi M (1993) Inhibition of ret tyrosine kinase activity by herbimycin A. Biochem Biophys Res Commun 195:208–214
Teter SA, Houry WA, Ang D, Tradler T, Rockabrand D, Fischer G, Blum P, Georgopoulos C, Hartl FU (1999) Polypeptide flux through bacterial Hsp70: DnaK cooperates with trigger factor in chaperoning nascent chains. Cell 97:755–765
Theyssen H, Schuster HP, Packschies L, Bukau B, Reinstein J (1996) The second step of ATP binding to DnaK induces peptide release. J Mol Biol 263:657–670
Thulasiraman V, Yang CF, Frydman J (1999) In vivo newly translated polypeptides are sequestered in a protected folding environment. EMBO J 18:85–95
Tilly K, McKittrick N, Zylicz M, Georgopoulos C (1983) The dnaK protein modulates the heat-shock response of Escherichia coli. Cell 34:641–646
Toft D, Gorski J (1966) A receptor molecule for estrogens: isolation from the rat uterus and preliminary characterization. Proc Natl Acad Sci 55:1574–1581
Tsubuki S, Saito Y, Kawashima S (1994) Purification and characterization of an endogenous inhibitor specific to the Z-Leu-Leu-Leu-MCA degrading activity in proteasome and its identification as heat-shock protein 90. FEBS Lett 344: 229–233
Uzawa M, Grams J, Madden B, Toft D, Salisbury JL (1995) Identification of a complex between centrin and heat shock proteins in CSF-arrested Xenopus oocytes and dissociation of the complex following oocyte activation. Dev Biol 171:51–59
Vaiskunaite R, Kozasa T, Voyno-Yasenetskaya TA (2001) Interaction between the G alpha subunit of heterotrimeric G(12) protein and Hsp90 is required for G alpha(12) signaling. J Biol Chem 276:46088–46093
van den Berg B, Ellis RJ, Dobson CM (1999) Effects of macromolecular crowding on protein folding and aggregation. EMBO J 18:6927–6933
Veldscholte J, Berrevoets CA, Zegers ND, van der Kwast TH, Grootegoed JA, Mulder E (1992) Hormone-induced dissociation of the androgen receptor-heat-shock protein complex: use of a new monoclonal antibody to distinguish transformed from nontransformed receptors. Biochemistry 31:7422–7430
Venema RC, Venema VJ, Ju H, Harris MB, Snead C, Jilling T, Dimitropoulou C, Maragoudakis ME, Catravas JD (2003) Novel complexes of guanylate cyclase with heat shock protein 90 and nitric oxide synthase. Am J Physiol Heart Circ Physiol 285:H669–H678
Vidal V, Qiu NH, Redfield B, Carlino A, Brot N, Weissbach H (1996) ATP hydrolysis is not required for the dissociation of a substance P BiP complex. Arch Biochem Biophys 330:314–318
Voisine C, Cheng YC, Ohlson M, Schilke B, Hoff K, Beinert H, Marszalek J, Craig EA (2001) Jac1, a mitochondrial J-type chaperone, is involved in the biogenesis of Fe/S clusters in Saccharomyces cerevisiae. Proc Natl Acad Sci 98:1483–1488
Wagner BJ, Margolis JW (1995) Age-dependent association of isolated bovine lens multicatalytic proteinase complex (proteasome) with heat-shock protein 90, an endogenous inhibitor. Arch Biochem Biophys 323:455–462
Waldron C, Jund R, Lacroute F (1974) The elongation rate of proteins of different molecular weight classes in yeast. FEBS Lett 46:11–16
Walter S, Buchner J (2002) Molecular chaperones-cellular machines for protein folding. Angew Chem Int Ed Engl 41:1098–1113
Warth R, Briand PA, Picard D (1997) Functional analysis of the yeast 40-kDa cyclophilin Cyp40 and its role for viability and steroid receptor regulation. Biol Chem 378:381–391
Wartmann M, Davis RJ (1994) The native structure of the activated Raf protein kinase is a membrane-bound multi-subunit complex. J Biol Chem 269:6695–6701
Weaver AJ, Sullivan WP, Felts SJ, Owen BA, Toft DO (2000) Crystal structure and activity of human p23, a heat shock protein 90 cochaperone. J Biol Chem 275:23045–23052
Wegele H, Haslbeck M, Reinstein J, Buchner J (2003a) Sti1 is a novel activator of the Ssa proteins. J Biol Chem 278:25970–25976
Wegele H, Muschler P, Bunck M, Reinstein J, Buchner J (2003b) Dissection of the contribution of individual domains to the ATPase mechanism of Hsp90. J Biol Chem 278:39303–39310
Wei J, Gaut JR, Hendershot LM (1995) In vitro dissociation of BiP-peptide complexes requires a conformational change in BiP after ATP binding but does not require ATP hydrolysis. J Biol Chem 270:26677–26682
Weikl T, Abelmann K, Buchner J (1999) An unstructured C-terminal region of the Hsp90 cochaperone p23 is important for its chaperone function. J Mol Biol 293:685–691
Weikl T, Muschler P, Richter K, Veit T, Reinstein J, Buchner J (2000) C-terminal regions of Hsp90 are important for trapping the nucleotide during the ATPase cycle. J Mol Biol 303:583–592
Welch WJ, Feramisco JR (1982) Purification of the major mammalian heat shock proteins. J Biol Chem 257: 14949–14959
Werner-Washburne M, Craig EA (1989) Expression of members of the Saccharomyces cerevisiae hsp70 multigene family. Genome 31:684–689
Whitelaw ML, Hutchison K, Perdew GH (1991) A 50-kDa cytosolic protein complexed with the 90-kDa heat shock protein (hsp90) is the same protein complexed with pp60v-src hsp90 in cells transformed by the Rous sarcoma virus. J Biol Chem 266:16436–16440
Whitesell L, Mimnaugh EG, De Costa B, Myers CE, Neckers LM (1994) Inhibition of heat shock protein HSP90-pp60v-src heteroprotein complex formation by benzoquinone ansamycins: essential role for stress proteins in oncogenic transformation. Proc Natl Acad Sci 91:8324–8328
Whitesell L, Shifrin SD, Schwab G, Neckers LM (1992) Benzoquinonoid ansamycins possess selective tumoricidal activity unrelated to src kinase inhibition. Cancer Res 52:1721–1728
Whitesell L, Sutphin PD, Pulcini EJ, Martinez JD, Cook PH (1998) The physical association of multiple molecular chaperone proteins with mutant p53 is altered by geldanamycin, an hsp90-binding agent. Mol Cell Biol 18: 1517–1524
Wickner S, Hoskins J, McKenney K (1991) Function of DnaJ and DnaK as chaperones in origin-specific DNA binding by RepA. Nature 350:165–167
Wigley DB, Davies GJ, Dodson EJ, Maxwell A, Dodson G (1991) Crystal structure of an N-terminal fragment of the DNA gyrase B protein. Nature 351:624–629
Wilbanks SM, Chen L, Tsuruta H, Hodgson KO, McKay DB (1995) Solution small-angle X-ray scattering study of the molecular chaperone Hsc70 and its subfragments. Biochemistry 34:12095–12106
Wilbanks SM, McKay DB (1995) How potassium affects the activity of the molecular chaperone Hsc70. II. Potassium binds specifically in the ATPase active site. J Biol Chem 270:2251–2257
Wilhelmsson A, Cuthill S, Denis M, Wikstrom AC, Gustafsson JA, Poellinger L (1990) The specific DNA binding activity of the dioxin receptor is modulated by the 90 kd heat shock protein. EMBO J 9:69–76
Wilson EM, Lea OA, French FS (1977) 9S binding protein for androgens and progesterone. Proc Natl Acad Sci 74:1960–1964
Xu M, Dittmar KD, Giannoukos G, Pratt WB, Simons SS, Jr (1998) Binding of hsp90 to the glucocorticoid receptor requires a specific 7-amino acid sequence at the amino terminus of the hormone-binding domain. J Biol Chem 273: 13918–13924
Xu W, Mimnaugh E, Rosser MF, Nicchitta C, Marcu M, Yarden Y, Neckers L (2001) Sensitivity of mature Erbb2 to geldanamycin is conferred by its kinase domain and is mediated by the chaperone protein Hsp90. J Biol Chem 276: 3702–3708
Xu Y, Lindquist S (1993) Heat-shock protein hsp90 governs the activity of pp60v-src kinase. Proc Natl Acad Sci 90:7074–7078
Xu Y, Singer MA, Lindquist S (1999) Maturation of the tyrosine kinase c-src as a kinase and as a substrate depends on the molecular chaperone Hsp90. Proc Natl Acad Sci 96:109–114
Young JC, Hartl FU (2000) Polypeptide release by Hsp90 involves ATP hydrolysis and is enhanced by the cochaperone p23. EMBO J 19:5930–5940
Young JC, Moarefi I, Hartl FU (2001) Hsp90: a specialized but essential protein-folding tool. J Cell Biol 154:267–273
Young JC, Obermann WM, Hartl FU (1998) Specific binding of tetratricopeptide repeat proteins to the C-terminal 12-kDa domain of hsp90. J Biol Chem 273:18007–18010
Young JC, Schneider C, Hartl FU (1997) In vitro evidence that hsp90 contains two independent chaperone sites. FEBS Lett 418:139–143
Yura T, Nagai H, Mori H (1993) Regulation of the heat-shock response in bacteria. Annu Rev Microbiol 47: 321–350
Zhang L, Hach A, Wang C (1998) Molecular mechanism governing heme signaling in yeast: a higher-order complex mediates heme regulation of the transcriptional activator HAP1. Mol Cell Biol 18:3819–3828
Zhao YG, Gilmore R, Leone G, Coffey MC, Weber B, Lee PW (2001) Hsp90 phosphorylation is linked to its chaperoning function. Assembly of the reovirus cell attachment protein. J Biol Chem 276:32822–32827
Zhu X, Zhao X, Burkholder WF, Gragerov A, Ogata CM, Gottesman ME, Hendrickson WA (1996) Structural analysis of substrate binding by the molecular chaperone DnaK. Science 272:1606–1614
Ziemiecki A, Catelli MG, Joab I, Moncharmont B (1986) Association of the heat shock protein hsp90 with steroid hormone receptors and tyrosine kinase oncogene products. Biochem Biophys Res Commun 138:1298–1307
Zylicz M, Ang D, Georgopoulos C (1987) The grpE protein of Escherichia coli. Purification and properties. J Biol Chem 262:17437–17442
Zylicz M, King FW, Wawrzynow A (2001) Hsp70 interactions with the p53 tumor suppressor protein. EMBO J 20: 4634–4638
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Wegele, H., Müller, L., Buchner, J. (2004). Hsp70 and Hsp90—a relay team for protein folding. In: Reviews of Physiology, Biochemistry and Pharmacology. Reviews of Physiology, Biochemistry and Pharmacology, vol 151. Springer, Berlin, Heidelberg. https://doi.org/10.1007/s10254-003-0021-1
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