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Bim and Bmf in tissue homeostasis and malignant disease

Oncogene volume 27, pages S41–S52 (2008)Cite this article

Abstract

Among all BH3-only proteins known to date, most information is available on the biological role and function of Bim (Bcl-2 interacting mediator of cell death)/BOD (Bcl-2 related ovarian death agonist), whereas little is still known about its closest relative, Bcl-2 modifying factor (Bmf). Although Bim has been implicated in the regulation of cell death induction in multiple cell types and tissues in response to a large number of stimuli, including growth factor or cytokine deprivation, calcium flux, ligation of antigen receptors on T and B cells, glucocorticoid or loss of adhesion, Bmf seems to play a more restricted role by supporting Bim in some of these cell death processes. This review aims to highlight similarities between Bim and Bmf function in apoptosis signaling and their role in normal development and disease.

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References

  • Adachi M, Zhao X, Imai K . (2005). Nomenclature of dynein light chain-linked BH3-only protein Bim isoforms. Cell Death Differ 12: 192–193.

    CAS  PubMed  Google Scholar 

  • Barron L, Knoechel B, Lohr J, Abbas AK . (2008). Cutting edge: contributions of apoptosis and anergy to systemic T cell tolerance. J Immunol 180: 2762–2766.

    CAS  PubMed  Google Scholar 

  • Biswas SC, Shi Y, Sproul A, Greene LA . (2007). Pro-apoptotic Bim induction in response to nerve growth factor deprivation requires simultaneous activation of three different death signaling pathways. J Biol Chem 282: 29368–29374.

    CAS  PubMed  Google Scholar 

  • Bouillet P, Cory S, Zhang L-C, Strasser A, Adams JM . (2001). Degenerative disorders caused by Bcl-2 deficiency are prevented by loss of its BH3-only antagonist Bim. Dev Cell 1: 645–653.

    CAS  PubMed  Google Scholar 

  • Bouillet P, Metcalf D, Huang DCS, Tarlinton DM, Kay TWH, Köntgen F et al. (1999). Proapoptotic Bcl-2 relative Bim required for certain apoptotic responses, leukocyte homeostasis, and to preclude autoimmunity. Science 286: 1735–1738.

    CAS  PubMed  Google Scholar 

  • Bouillet P, Purton JF, Godfrey DI, Zhang L-C, Coultas L, Puthalakath H et al. (2002). BH3-only Bcl-2 family member Bim is required for apoptosis of autoreactive thymocytes. Nature 415: 922–926.

    CAS  PubMed  Google Scholar 

  • Cai B, Chang SH, Becker EB, Bonni A, Xia Z . (2006). p38 MAP kinase mediates apoptosis through phosphorylation of BimEL at Ser-65. J Biol Chem 281: 25215–25222.

    CAS  PubMed  Google Scholar 

  • Certo M, Moore Vdel G, Nishino M, Wei G, Korsmeyer S, Armstrong SA et al. (2006). Mitochondria primed by death signals determine cellular addiction to antiapoptotic BCL-2 family members. Cancer Cell 9: 351–365.

    CAS  PubMed  Google Scholar 

  • Chen D, Zhou Q . (2004). Caspase cleavage of BimEL triggers a positive feedback amplification of apoptotic signaling. Proc Natl Acad Sci USA 101: 1235–1240.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Chen L, Willis SN, Wei A, Smith BJ, Fletcher JI, Hinds MG et al. (2005). Differential targeting of prosurvival Bcl-2 proteins by their BH3-only ligands allows complementary apoptotic function. Mol Cell 17: 393–403.

    CAS  PubMed  Google Scholar 

  • Cohen PL, Eisenberg RA . (1991). Lpr and gld: single gene models of systemic autoimmunity and lymphoproliferative disease. Annu Rev Immunol 9: 243–269.

    CAS  PubMed  Google Scholar 

  • Corazza N, Jakob S, Schaer C, Frese S, Keogh A, Stroka D et al. (2006). TRAIL receptor-mediated JNK activation and Bim phosphorylation critically regulate Fas-mediated liver damage and lethality. J Clin Invest 116: 2493–2499.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Coultas L, Bouillet P, Loveland KL, Meachem S, Perlman H, Adams JM et al. (2005). Concomitant loss of proapoptotic BH3-only Bcl-2 antagonists Bik and Bim arrests spermatogenesis. EMBO J 24: 3963–3973.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Cragg MS, Jansen ES, Cook M, Harris C, Strasser A, Scott CL . (2008). Treatment of B-RAF mutant human tumor cells with a MEK inhibitor requires Bim and is enhanced by a BH3 mimetic. J Clin Invest 118: 3651–3659.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Cragg MS, Kuroda J, Puthalakath H, Huang DC, Strasser A . (2007). Gefitinib-induced killing of NSCLC cell lines expressing mutant EGFR requires BIM and can be enhanced by BH3 mimetics. PLoS Med 4: 1681–1689; discussion 1690.

    CAS  PubMed  Google Scholar 

  • Czabotar PE, Lee EF, van Delft MF, Day CL, Smith BJ, Huang DC et al. (2007). Structural insights into the degradation of Mcl-1 induced by BH3 domains. Proc Natl Acad Sci USA 104: 6217–6222.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Del Gaizo Moore V, Brown JR, Certo M, Love TM, Novina CD, Letai A . (2007). Chronic lymphocytic leukemia requires BCL2 to sequester prodeath BIM, explaining sensitivity to BCL2 antagonist ABT-737. J Clin Invest 117: 112–121.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Deng J, Shimamura T, Perera S, Carlson NE, Cai D, Shapiro GI et al. (2007). Proapoptotic BH3-only BCL-2 family protein BIM connects death signaling from epidermal growth factor receptor inhibition to the mitochondrion. Cancer Res 67: 11867–11875.

    CAS  PubMed  Google Scholar 

  • Dijkers PF, Medema RH, Lammers JW, Koenderman L, Coffer PJ . (2000). Expression of the pro-apoptotic Bcl-2 family member Bim is regulated by the forkhead transcription factor FKHR-L1. Curr Biol 10: 1201–1204.

    CAS  PubMed  Google Scholar 

  • Egle A, Harris AW, Bath ML, O'Reilly L, Cory S . (2004a). VavP-Bcl2 transgenic mice develop follicular lymphoma preceded by germinal center hyperplasia. Blood 103: 2276–2283.

    CAS  PubMed  Google Scholar 

  • Egle A, Harris AW, Bouillet P, Cory S . (2004b). Bim is a suppressor of Myc-induced mouse B cell leukemia. Proc Natl Acad Sci USA 101: 6164–6169.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Eischen CM, Woo D, Roussel MF, Cleveland JL . (2001). Apoptosis triggered by myc-induced suppression of Bcl-XL or Bcl-2 Is bypassed during lymphomagenesis. Mol Cell Biol 21: 5063–5070.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Enders A, Bouillet P, Puthalakath H, Xu Y, Tarlinton DM, Strasser A . (2003). Loss of the pro-apoptotic BH3-only Bcl-2 family member Bim inhibits BCR stimulation-induced apoptosis and deletion of autoreactive B cells. J Exp Med 198: 1119–1126.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Erlacher M, Labi V, Manzl C, Bock G, Tzankov A, Hacker G et al. (2006). Puma cooperates with Bim, the rate-limiting BH3-only protein in cell death during lymphocyte development, in apoptosis induction. J Exp Med 203: 2939–2951.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Fischer SF, Bouillet P, O'Donnell K, Light A, Tarlinton DM, Strasser A . (2007). Proapoptotic BH3-only protein Bim is essential for developmentally programmed death of germinal center-derived memory B cells and antibody-forming cells. Blood 110: 3978–3984.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Gavathiotis E, Suzuki M, Davis ML, Pitter K, Bird GH, Katz SG et al. (2008). BAX activation is initiated at a novel interaction site. Nature 455: 1076–1081.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Herold MJ, Zeitz J, Pelzer C, Kraus C, Peters A, Wohlleben G et al. (2006). The stability and anti-apoptotic function of A1 are controlled by its C terminus. J Biol Chem 281: 13663–13671.

    CAS  PubMed  Google Scholar 

  • Hershko T, Ginsberg D . (2004). Up-regulation of Bcl-2 homology 3 (BH3)-only proteins by E2F1 mediates apoptosis. J Biol Chem 279: 8627–8634.

    CAS  PubMed  Google Scholar 

  • Hildeman DA, Zhu Y, Mitchell TC, Bouillet P, Strasser A, Kappler J et al. (2002). Activated T cell death in vivo mediated by pro-apoptotic Bcl-2 family member, Bim. Immunity 16: 759–767.

    CAS  PubMed  Google Scholar 

  • Hsu SY, Lin P, Hsueh AJW . (1998). BOD (Bcl-2-related ovarian death gene) is an ovarian BH3 domain-containing proapoptotic Bcl-2 protein capable of dimerization with diverse antiapoptotic Bcl-2 members. Mol Endocrinol 12: 1432–1440.

    CAS  PubMed  Google Scholar 

  • Hubner A, Barrett T, Flavell RA, Davis RJ . (2008). Multisite phosphorylation regulates Bim stability and apoptotic activity. Mol Cell 30: 415–425.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Hughes PD, Belz GT, Fortner KA, Budd RC, Strasser A, Bouillet P . (2008). Apoptosis regulators Fas and Bim cooperate in shutdown of chronic immune responses and prevention of autoimmunity. Immunity 28: 197–205.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Hutcheson J, Scatizzi JC, Siddiqui AM, Haines III GK, Wu T, Li QZ et al. (2008). Combined deficiency of proapoptotic regulators Bim and Fas results in the early onset of systemic autoimmunity. Immunity 28: 206–217.

    CAS  PubMed  Google Scholar 

  • Inoue S, Riley J, Gant TW, Dyer MJ, Cohen GM . (2007). Apoptosis induced by histone deacetylase inhibitors in leukemic cells is mediated by Bim and Noxa. Leukemia 21: 1773–1782.

    CAS  PubMed  Google Scholar 

  • Inta I, Paxian S, Maegele I, Zhang W, Pizzi M, Spano P et al. (2006). Bim and Noxa are candidates to mediate the deleterious effect of the NF-kappa B subunit RelA in cerebral ischemia. J Neurosci 26: 12896–12903.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Jette CA, Flanagan AM, Ryan J, Pyati UJ, Carbonneau S, Stewart RA et al. (2008). BIM and other BCL-2 family proteins exhibit cross-species conservation of function between zebrafish and mammals. Cell Death Differ 15: 1063–1072.

    CAS  PubMed  Google Scholar 

  • Kratz E, Eimon PM, Mukhyala K, Stern H, Zha J, Strasser A et al. (2006). Functional characterization of the Bcl-2 gene family in the zebrafish. Cell Death Differ 13: 1631–1640.

    CAS  PubMed  Google Scholar 

  • Kuroda J, Puthalakath H, Cragg MS, Kelly PN, Bouillet P, Huang DC et al. (2006). Bim and Bad mediate imatinib-induced killing of Bcr/Abl+ leukemic cells, and resistance due to their loss is overcome by a BH3 mimetic. Proc Natl Acad Sci USA 103: 14907–14912.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Kuwana T, Bouchier-Hayes L, Chipuk JE, Bonzon C, Sullivan BA, Green DR et al. (2005). BH3 domains of BH3-only proteins differentially regulate Bax-mediated mitochondrial membrane permeabilization both directly and indirectly. Mol Cell 17: 525–535.

    CAS  PubMed  Google Scholar 

  • Labi V, Erlacher M, Kiessling S, Manzl C, Frenzel A, O'Reilly L et al. (2008a). Loss of the BH3-only protein Bmf impairs B cell homeostasis and accelerates gamma irradiation-induced thymic lymphoma development. J Exp Med 205: 641–655.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Labi V, Erlacher M, Kiessling S, Villunger A . (2006). BH3-only proteins in cell death initiation, malignant disease and anticancer therapy. Cell Death Differ 13: 1325–1338.

    CAS  PubMed  Google Scholar 

  • Labi V, Grespi F, Baumgartner F, Villunger A . (2008b). Targeting the Bcl-2-regulated apoptosis pathway by BH3 mimetics: a breakthrough in anticancer therapy? Cell Death Differ 15: 977–987.

    CAS  PubMed  Google Scholar 

  • Lei K, Davis RJ . (2003). JNK phosphorylation of Bim-related members of the Bcl2 family induces Bax-dependent apoptosis. Proc Natl Acad Sci USA 100: 2432–2437.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Ley R, Ewings KE, Hadfield K, Cook SJ . (2005). Regulatory phosphorylation of Bim: sorting out the ERK from the JNK. Cell Death Differ 12: 1008–1014.

    CAS  PubMed  Google Scholar 

  • Li R, Moudgil T, Ross HJ, Hu HM . (2005). Apoptosis of non-small-cell lung cancer cell lines after paclitaxel treatment involves the BH3-only proapoptotic protein Bim. Cell Death Differ 12: 292–303.

    CAS  PubMed  Google Scholar 

  • Liu X, Dai S, Zhu Y, Marrack P, Kappler JW . (2003). The structure of a Bcl-xL/Bim fragment complex: implications for Bim function. Immunity 19: 341–352.

    CAS  PubMed  Google Scholar 

  • Mackus WJ, Kater AP, Grummels A, Evers LM, Hooijbrink B, Kramer MH et al. (2005). Chronic lymphocytic leukemia cells display p53-dependent drug-induced Puma upregulation. Leukemia 19: 427–434.

    CAS  PubMed  Google Scholar 

  • Mailleux AA, Overholtzer M, Schmelzle T, Bouillet P, Strasser A, Brugge JS . (2007). BIM regulates apoptosis during mammary ductal morphogenesis, and its absence reveals alternative cell death mechanisms. Dev Cell 12: 221–234.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Matsui H, Asou H, Inaba T . (2007). Cytokines direct the regulation of Bim mRNA stability by heat-shock cognate protein 70. Mol Cell 25: 99–112.

    CAS  PubMed  Google Scholar 

  • Mei Y, Du W, Yang Y, Wu M . (2005). Puma(*)Mcl-1 interaction is not sufficient to prevent rapid degradation of Mcl-1. Oncogene 24: 7224–7237.

    CAS  PubMed  Google Scholar 

  • Mestre-Escorihuela C, Rubio-Moscardo F, Richter JA, Siebert R, Climent J, Fresquet V et al. (2007). Homozygous deletions localize novel tumor suppressor genes in B-cell lymphomas. Blood 109: 271–280.

    CAS  PubMed  Google Scholar 

  • Morales AA, Gutman D, Lee KP, Boise LH . (2008). BH3-only proteins Noxa, Bmf, and Bim are necessary for arsenic trioxide-induced cell death in myeloma. Blood 111: 5152–5162.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Morales AA, Olsson A, Celsing F, Osterborg A, Jondal M, Osorio LM . (2004). Expression and transcriptional regulation of functionally distinct Bmf isoforms in B-chronic lymphocytic leukemia cells. Leukemia 18: 41–47.

    CAS  PubMed  Google Scholar 

  • O'Connor L, Strasser A, O'Reilly LA, Hausmann G, Adams JM, Cory S et al. (1998). Bim: a novel member of the Bcl-2 family that promotes apoptosis. EMBO J 17: 384–395.

    CAS  PubMed  PubMed Central  Google Scholar 

  • O'Donnell KA, Wentzel EA, Zeller KI, Dang CV, Mendell JT . (2005). c-Myc-regulated microRNAs modulate E2F1 expression. Nature 435: 839–843.

    Article  CAS  PubMed  Google Scholar 

  • O'Reilly LA, Cullen L, Visvader J, Lindeman G, Print C, Bath ML et al. (2000). The pro-apoptotic BH3-only protein Bim is expressed in hemopoietic, epithelial, neuronal and germ cells. Am J Pathol 157: 449–461.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Oliveira JB, Bidere N, Niemela JE, Zheng L, Sakai K, Nix CP et al. (2007). NRAS mutation causes a human autoimmune lymphoproliferative syndrome. Proc Natl Acad Sci USA 104: 8953–8958.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Oliver PM, Vass T, Kappler J, Marrack P . (2006). Loss of the proapoptotic protein, Bim, breaks B cell anergy. J Exp Med 203: 731–741.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Pellegrini M, Belz G, Bouillet P, Strasser A . (2003). Shutdown of an acute T cell immune response to viral infection is mediated by the proapoptotic Bcl-2 homology 3-only protein Bim. Proc Natl Acad Sci USA 100: 14175–14180.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Pellegrini M, Bouillet P, Robati M, Belz GT, Davey GM, Strasser A . (2004). Loss of Bim increases T cell production and function in interleukin 7 receptor-deficient mice. J Exp Med 200: 1189–1195.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Ploner C, Rainer J, Niederegger H, Eduardoff M, Villunger A, Geley S et al. (2008). The BCL2 rheostat in glucocorticoid-induced apoptosis of acute lymphoblastic leukemia. Leukemia 22: 370–377.

    CAS  PubMed  Google Scholar 

  • Ponassi R, Biasotti B, Tomati V, Bruno S, Poggi A, Malacarne D et al. (2008). A novel Bim-BH3-derived Bcl-XL inhibitor: biochemical characterization, in vitro, in vivo and ex-vivo anti-leukemic activity. Cell Cycle 7: 3211–3224.

    CAS  PubMed  Google Scholar 

  • Putcha GV, Le S, Frank S, Besirli CG, Clark K, Chu B et al. (2003). JNK-mediated BIM phosphorylation potentiates BAX-dependent apoptosis. Neuron 38: 899–914.

    CAS  PubMed  Google Scholar 

  • Puthalakath H, Huang DCS, O'Reilly LA, King SM, Strasser A . (1999). The pro-apoptotic activity of the Bcl-2 family member Bim is regulated by interaction with the dynein motor complex. Mol Cell 3: 287–296.

    CAS  PubMed  Google Scholar 

  • Puthalakath H, O'Reilly LA, Gunn P, Lee L, Kelly PN, Huntington ND et al. (2007). ER stress triggers apoptosis by activating BH3-only protein Bim. Cell 129: 1337–1349.

    CAS  PubMed  Google Scholar 

  • Puthalakath H, Strasser A . (2002). Keeping killers on a tight leash: transcriptional and post-translational control of the pro-apoptotic activity of BH3-only proteins. Cell Death Differ 9: 505–512.

    CAS  PubMed  Google Scholar 

  • Puthalakath H, Villunger A, O'Reilly LA, Beaumont JG, Coultas L, Cheney RE et al. (2001). Bmf: a pro-apoptotic BH3-only protein regulated by interaction with the myosin V actin motor complex, activated by anoikis. Science 293: 1829–1832.

    CAS  PubMed  Google Scholar 

  • Ralston A, Rossant J . (2006). How signaling promotes stem cell survival: trophoblast stem cells and Shp2. Dev Cell 10: 275–276.

    CAS  PubMed  Google Scholar 

  • Ramjaun AR, Tomlinson S, Eddaoudi A, Downward J . (2007). Upregulation of two BH3-only proteins, Bmf and Bim, during TGF beta-induced apoptosis. Oncogene 26: 970–981.

    CAS  PubMed  Google Scholar 

  • Rodin SN, Parkhomchuk DV, Rodin AS, Holmquist GP, Riggs AD . (2005). Repositioning-dependent fate of duplicate genes. DNA Cell Biol 24: 529–542.

    CAS  PubMed  Google Scholar 

  • Romano S, Mallardo M, Chiurazzi F, Bisogni R, D'Angelillo A, Liuzzi R et al. (2008). The effect of FK506 on transforming growth factor beta signaling and apoptosis in chronic lymphocytic leukemia B cells. Haematologica 93: 1039–1048.

    CAS  PubMed  Google Scholar 

  • Schmelzle T, Mailleux AA, Overholtzer M, Carroll JS, Solimini NL, Lightcap ES et al. (2007). Functional role and oncogene-regulated expression of the BH3-only factor Bmf in mammary epithelial anoikis and morphogenesis. Proc Natl Acad Sci USA 104: 3787–3792.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Schmutte C, Tombline G, Rhiem K, Sadoff MM, Schmutzler R, von Deimling A et al. (1999). Characterization of the human Rad51 genomic locus and examination of tumors with 15q14-15 loss of heterozygosity (LOH). Cancer Res 59: 4564–4569.

    CAS  PubMed  Google Scholar 

  • Sinicrope FA, Rego RL, Okumura K, Foster NR, O'Connell MJ, Sargent DJ et al. (2008). Prognostic impact of bim, puma, and noxa expression in human colon carcinomas. Clin Cancer Res 14: 5810–5818.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Stahl M, Dijkers PF, Kops GJ, Lens SM, Coffer PJ, Burgering BM et al. (2002). The forkhead transcription factor FoxO regulates transcription of p27Kip1 and Bim in response to IL-2. J Immunol 168: 5024–5031.

    CAS  PubMed  Google Scholar 

  • Strasser A . (2005). The role of BH3-only proteins in the immune system. Nat Rev Immunol 5: 189–200.

    CAS  PubMed  Google Scholar 

  • Sunters A, Fernandez de Mattos S, Stahl M, Brosens JJ, Zoumpoulidou G, Saunders CA et al. (2003). FoxO3a transcriptional regulation of Bim controls apoptosis in paclitaxel-treated breast cancer cell lines. J Biol Chem 278: 49795–49805.

    CAS  PubMed  Google Scholar 

  • Tagawa H, Karnan S, Suzuki R, Matsuo K, Zhang X, Ota A et al. (2005). Genome-wide array-based CGH for mantle cell lymphoma: identification of homozygous deletions of the proapoptotic gene BIM. Oncogene 24: 1348–1358.

    CAS  PubMed  Google Scholar 

  • Tan TT, Degenhardt K, Nelson DA, Beaudoin B, Nieves-Neira W, Bouillet P et al. (2005). Key roles of BIM-driven apoptosis in epithelial tumors and rational chemotherapy. Cancer Cell 7: 227–238.

    CAS  PubMed  Google Scholar 

  • Tse C, Shoemaker AR, Adickes J, Anderson MG, Chen J, Jin S et al. (2008). ABT-263: a potent and orally bioavailable Bcl-2 family inhibitor. Cancer Res 68: 3421–3428.

    CAS  PubMed  Google Scholar 

  • van Delft MF, Wei AH, Mason KD, Vandenberg CJ, Chen L, Czabotar PE et al. (2006). The BH3 mimetic ABT-737 targets selective Bcl-2 proteins and efficiently induces apoptosis via Bak/Bax if Mcl-1 is neutralized. Cancer Cell 10: 389–399.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Veis DJ, Sentman CL, Bach EA, Korsmeyer SJ . (1993). Expression of the Bcl-2 protein in murine and human thymocytes and in peripheral T lymphocytes. J Immunol 151: 2546–2554.

    CAS  PubMed  Google Scholar 

  • Ventura A, Young AG, Winslow MM, Lintault L, Meissner A, Erkeland SJ et al. (2008). Targeted deletion reveals essential and overlapping functions of the miR-17 through 92 family of miRNA clusters. Cell 132: 875–886.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Watanabe-Fukunaga R, Brannan CI, Copeland NG, Jenkins NA, Nagata S . (1992). Lymphoproliferation disorder in mice explained by defects in Fas antigen that mediates apoptosis. Nature 356: 314–317.

    CAS  PubMed  Google Scholar 

  • Weant AE, Michalek RD, Khan IU, Holbrook BC, Willingham MC, Grayson JM . (2008). Apoptosis regulators Bim and Fas function concurrently to control autoimmunity and CD8+ T cell contraction. Immunity 28: 218–230.

    CAS  PubMed  Google Scholar 

  • Weber A, Paschen SA, Heger K, Wilfling F, Frankenberg T, Bauerschmitt H et al. (2007). BimS-induced apoptosis requires mitochondrial localization but not interaction with anti-apoptotic Bcl-2 proteins. J Cell Biol 177: 625–636.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Wick W, Petersen I, Schmutzler RK, Wolfarth B, Lenartz D, Bierhoff E et al. (1996). Evidence for a novel tumor suppressor gene on chromosome 15 associated with progression to a metastatic stage in breast cancer. Oncogene 12: 973–978.

    CAS  PubMed  Google Scholar 

  • Willis SN, Fletcher JI, Kaufmann T, van Delft MF, Chen L, Czabotar PE et al. (2007). Apoptosis initiated when BH3 ligands engage multiple Bcl-2 homologs, not Bax or Bak. Science 315: 856–859.

    CAS  PubMed  Google Scholar 

  • Wojciechowski S, Tripathi P, Bourdeau T, Acero L, Grimes HL, Katz JD et al. (2007). Bim/Bcl-2 balance is critical for maintaining naive and memory T cell homeostasis. J Exp Med 204: 1665–1675.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Xiao C, Srinivasan L, Calado DP, Patterson HC, Zhang B, Wang J et al. (2008). Lymphoproliferative disease and autoimmunity in mice with increased miR-17-92 expression in lymphocytes. Nat Immunol 9: 405–414.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Yamamura Y, Lee WL, Inoue K, Ida H, Ito Y . (2006). RUNX3 cooperates with FoxO3a to induce apoptosis in gastric cancer cells. J Biol Chem 281: 5267–5276.

    CAS  PubMed  Google Scholar 

  • Youle RJ, Strasser A . (2008). The BCL-2 protein family: opposing activities that mediate cell death. Nat Rev Mol Cell Biol 9: 47–59.

    CAS  PubMed  Google Scholar 

  • Zantl N, Weirich G, Zall H, Seiffert BM, Fischer SF, Kirschnek S et al. (2007). Frequent loss of expression of the pro-apoptotic protein Bim in renal cell carcinoma: evidence for contribution to apoptosis resistance. Oncogene 26: 7038–7048.

    CAS  PubMed  Google Scholar 

  • Zhang Y, Adachi M, Kawamura R, Imai K . (2006a). Bmf is a possible mediator in histone deacetylase inhibitors FK228 and CBHA-induced apoptosis. Cell Death Differ 13: 129–140.

    CAS  PubMed  Google Scholar 

  • Zhang Y, Adachi M, Kawamura R, Zou HC, Imai K, Hareyama M et al. (2006b). Bmf contributes to histone deacetylase inhibitor-mediated enhancing effects on apoptosis after ionizing radiation. Apoptosis 11: 1349–1357.

    CAS  PubMed  Google Scholar 

  • Zhu Y, Swanson BJ, Wang M, Hildeman DA, Schaefer BC, Liu X et al. (2004). Constitutive association of the proapoptotic protein Bim with Bcl-2-related proteins on mitochondria in T cells. Proc Natl Acad Sci USA 101: 7681–7686.

    CAS  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

The work in our laboratories is supported by fellowships and grants from the Austrian Science Fund (FWF): Y212-B13 START, P19481-B12, L488-B13, the Doctoral College MCBO, the SFB021, the Association for International Cancer Research (AICR), EU-FP7 (ApopTrain), the Austrian National Bank (OeNB) # 109900 and the Tyrolean Science Fund (TWF). We apologize to the many scientists in this field whose excellent research was not cited, but was only referred to indirectly through reviews.

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  1. Laboratory for Immunological and Molecular Cancer Research, University Hospital Salzburg, Salzburg, Austria,

    J D Piñon & A Egle

  2. Division of Developmental Immunology, Biocenter, Innsbruck Medical University, Innsbruck, Austria

    V Labi & A Villunger

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Piñon, J., Labi, V., Egle, A. et al. Bim and Bmf in tissue homeostasis and malignant disease. Oncogene 27 (Suppl 1), S41–S52 (2008). https://doi.org/10.1038/onc.2009.42

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