nach oben

Journal of Cancer Research and Clinical Oncology

Erschienen in:

01.09.2009 | Original Paper

A novel role for DYX1C1, a chaperone protein for both Hsp70 and Hsp90, in breast cancer

Erschienen in: Journal of Cancer Research and Clinical Oncology | Ausgabe 9/2009

Einloggen, um Zugang zu erhalten

Abstract

Aims

With three consecutive tetratricopeptide repeat (TPR) motifs at its C-terminus essential for neuronal migration, and a p23 domain at its N-terminus, DYX1C1 was the first gene proposed to have a role in developmental dyslexia. In this study, we attempted to identify the potential interaction of DYX1C1 and heat shock protein, and the role of DYX1C1 in breast cancer.

Main methods

GST pull-down, a yeast two-hybrid system, RT-PCR, site-directed mutagenesis approach.

Key findings

Our study initially confirmed DYX1C1, a dyslexia related protein, could interact with Hsp70 and Hsp90 via GST pull-down and a yeast two-hybrid system. And we verified that EEVD, the C-terminal residues of DYX1C1, is responsible for the identified association. Further, DYX1C1 mRNA was significantly overexpressed in malignant breast tumor, linking with the up-regulated expression of Hsp70 and Hsp90.

Significance

These results suggest that DYX1C1 is a novel Hsp70 and Hsp90-interacting co-chaperone protein and its expression is associated with malignancy.

Adamson ED, Mercola D (2002) Egr1 transcription factor: multiple roles in prostate tumor cell growth and survival. Tumour Biol 23(2):93–102PubMedCrossRef

Beere HM (2004) “The stress of dying”: the role of heat shock proteins in the regulation of apoptosis. J Cell Sci 117:2641–2651PubMedCrossRef

Beere HM, Green DR (2001) Stress management—heat shock protein-70 and the regulation of apoptosis. Trends Cell Biol 11:6–10PubMedCrossRef

Begley LA, MacDonald JW, Day ML, Macoska JA (2007) CXCL12 activates a robust transcriptional response in human prostate epithelial cells. J Biol Chem 282:26767–26774PubMedCrossRef

Blatch GL, Lassle M (1999) The tetratricopeptide repeat: a structural motif mediating protein–protein interactions. Bioessays 21:932–939PubMedCrossRef

Cabioglu N, Summy J, Miller C et al (2005) CXCL-12/stromal cell-derived factor-1alpha transactivates HER2-neu in breast cancer cells by a novel pathway involving Src kinase activation. Cancer Res 65:6493–6497PubMedCrossRef

Calderwood SK, Khaleque MA, Sawyer DB, Ciocca DR (2006) Heat shock proteins in cancer: chaperones of tumorigenesis. Trends Biochem Sci 31:164–172PubMedCrossRef

Cao Q, Chen J, Zhu L et al (2006) A testis-specific and testis developmentally regulated tumor protein D52 (TPD52)-like protein TPD52L3/hD55 interacts with TPD52 family proteins. Biochem Biophys Res Commun 344:798–806PubMedCrossRef

Carrigan PE, Sikkink LA, Smith DF, Ramirez-Alvarado M (2006) Domain:domain interactions within Hop, the Hsp70/Hsp90 organizing protein, are required for protein stability and structure. Protein Sci 15:522–532PubMedCrossRef

Chaix Y, Albaret JM, Brassard C et al (2007) Motor impairment in dyslexia: the influence of attention disorders. Eur J Paediatr Neurol 11:368–374PubMedCrossRef

D’Andrea LD, Regan L (2003) TPR proteins: the versatile helix. Trends Biochem Sci 28:655–662PubMedCrossRef

Doong H, Vrailas A, Kohn EC (2002) What’s in the ‘BAG’? A functional domain analysis of the BAG-family proteins. Cancer Lett 188:25–32PubMedCrossRef

Elston CW, Ellis IO (1991) Pathological prognostic factors in breast cancer I. The value of histological grade in breast cancer: experience from a large study with long-term follow-up. Histopathology 19:403–410PubMedCrossRef

Freeman BC, Yamamoto KR (2002) Disassembly of transcriptional regulatory complexes by molecular chaperones. Science 296:2232–2235PubMedCrossRef

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 14:422–434PubMed

Frydman J, Hohfeld J (1997) Chaperones get in touch: the Hip–Hop connection. Trends Biochem Sci 22:87–92PubMedCrossRef

Gething MJ, Sambrook J (1992) Protein folding in the cell. Nature 355:33–45PubMedCrossRef

Hartl FU, Hayer-Hartl M (2002) Molecular chaperones in the cytosol: from nascent chain to folded protein. Science 295:1852–1858PubMedCrossRef

Jameel A, Skilton RA, Campbell TA, Chander SK, Coombes RC, Luqmani YA (1992) Clinical and biological significance of HSP89 alpha in human breast cancer. Int J Cancer 50:409–415PubMedCrossRef

Johnson JL, Toft DO (1994) A novel chaperone complex for steroid receptors involving heat shock proteins, immunophilins, and p23. J Biol Chem 269:24989–24993PubMed

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(3):1956–1963PubMed

Jolly C, Morimoto RI (2000) Role of the heat shock response and molecular chaperones in oncogenesis and cell death. J Nat Cancer Inst 92:1564–1572PubMedCrossRef

Kaur J, Ralhan R (1995) Differential expression of 70-kDa heat shock-protein in human oral tumorigenesis. Int J Cancer 63:774–779PubMedCrossRef

Kim YJ, Huh JW, Kim DS et al (2009) Molecular characterization of the DYX1C1 gene and its application as a cancer biomarker. J Cancer Res Clin Oncol 135(2):265–270PubMedCrossRef

Krebs J, Saremaslani P, Caduff R (2002) ALG-2: a Ca²⁺-binding modulator protein involved in cell proliferation and in cell death. Biochim Biophys Acta 1600:68–73PubMed

Lane DP, Midgley C, Hupp T (1993) Tumour suppressor genes and molecular chaperones. Philos Trans R Soc B 339:369–372 discussion 72–73CrossRef

Li W, Jin K, Nagayama T et al (2000) Increased expression of apoptosis-linked gene 2 (ALG2) in the rat brain after temporary focal cerebral ischemia. Neuroscience 96:161–168PubMedCrossRef

Marino C, Giorda R, Luisa Lorusso M et al (2005) A family-based association study does not support DYX1C1 on 15q21.3 as a candidate gene in developmental dyslexia. Eur J Hum Genet 13:491–499PubMedCrossRef

Miyata Y, Chambraud B, Radanyi C, et al. (1997) Phosphorylation of the immunosuppressant FK506-binding protein FKBP52 by casein kinase II: regulation of HSP90-binding activity of FKBP52. Proceedings of the National Academy of Sciences 94, 14500-5

Moczko M, Bomer U, Kubrich M, Zufall N, Honlinger A, Pfanner N (1997) The intermembrane space domain of mitochondrial Tom22 functions as a trans binding site for preproteins with N-terminal targeting sequences. Mol Cell Biol 17:6574–6584PubMed

Mollerup J, Berchtold MW (2005) The co-chaperone p23 is degraded by caspases and the proteasome during apoptosis. FEBS Lett 579:4187–4192PubMedCrossRef

Neckers L, Neckers K (2002) Heat-shock protein 90 inhibitors as novel cancer chemotherapeutic agents. Expert Opin Emerg Drugs 7:277–288PubMedCrossRef

Neckers L, Schulte TW, Mimnaugh E (1999) Geldanamycin as a potential anti-cancer agent: its molecular target and biochemical activity. Invest New Drugs 17:361–373PubMedCrossRef

Nollen EA, Morimoto RI (2002) Chaperoning signaling pathways: molecular chaperones as stress-sensing ‘heat shock’ proteins. J Cell Sci 115:2809–2816PubMed

Parcellier A, Gurbuxani S, Schmitt E, Solary E, Garrido C (2003) Heat shock proteins, cellular chaperones that modulate mitochondrial cell death pathways. Biochem Biophys Res Commun 304:505–512PubMedCrossRef

Parsell DA, Lindquist S (1993) The function of heat-shock proteins in stress tolerance: degradation and reactivation of damaged proteins. Annu Rev Genet 27:437–496PubMedCrossRef

Ramus F (2004) Neurobiology of dyslexia: a reinterpretation of the data. Trends Neurosci 27:720–726PubMedCrossRef

Santarosa M, Favaro D, Quaia M, Galligioni E (1997) Expression of heat shock protein 72 in renal cell carcinoma: possible role and prognostic implications in cancer patients. Eur J Cancer 33:873–877PubMedCrossRef

Scheufler C, Brinker A, Bourenkov G et al (2000) Structure of TPR domain-peptide complexes: critical elements in the assembly of the Hsp70-Hsp90 multichaperone machine. Cell 101:199–210PubMedCrossRef

Sreedhar AS, Csermely P (2004) Heat shock proteins in the regulation of apoptosis: new strategies in tumor therapy: a comprehensive review. Pharmacol Ther 101:227–257PubMedCrossRef

Steensgaard P, Garre M, Muradore I et al (2004) Sgt1 is required for human kinetochore assembly. EMBO Rep 5:626–631PubMedCrossRef

Stuart JK, Myszka DG, Joss L et al (1998) Characterization of interactions between the anti-apoptotic protein BAG-1 and Hsc70 molecular chaperones. J Biol Chem 273:22506–22514PubMedCrossRef

Sullivan WP, Owen BA, Toft DO (2002) The influence of ATP and p23 on the conformation of hsp90. J Biol Chem 277:45942–45948PubMedCrossRef

Taipale M, Kaminen N, Nopola-Hemmi J et al (2003) A candidate gene for developmental dyslexia encodes a nuclear tetratricopeptide repeat domain protein dynamically regulated in brain. Proceedings of the National Academy of Sciences 100, 11553-8

Takayama S, Sato T, Krajewski S et al (1995) Cloning and functional analysis of BAG-1: a novel Bcl-2-binding protein with anti-cell death activity. Cell 80:279–284PubMedCrossRef

Threlkeld SW, McClure MM, Bai J et al (2007) Developmental disruptions and behavioral impairments in rats following in utero RNAi of Dyx1c1. Brain Res Bull 71:508–514PubMedCrossRef

Tzamarias D, Struhl K (1995) Distinct TPR motifs of Cyc8 are involved in recruiting the Cyc8-Tup1 corepressor complex to differentially regulated promoters. Genes Dev 9:821–831PubMedCrossRef

Wang Y, Paramasivam M, Thomas A et al (2006) DYX1C1 functions in neuronal migration in developing neocortex. Neuroscience 143:515–522PubMedCrossRef

Wong HR, Wispe JR (1997) The stress response and the lung. Am J Physiol 273:L1–L9PubMed

Yufu Y, Nishimura J, Nawata H (1992) High constitutive expression of heat shock protein 90 alpha in human acute leukemia cells. Leuk Res 16:597–605PubMedCrossRef

Zeke T, Morrice N, Vazquez-Martin C, Cohen PT (2005) Human protein phosphatase 5 dissociates from heat-shock proteins and is proteolytically activated in response to arachidonic acid and the microtubule-depolymerizing drug nocodazole. Biochem J 385:45–56PubMedCrossRef

Titel: A novel role for DYX1C1, a chaperone protein for both Hsp70 and Hsp90, in breast cancer
Publikationsdatum: 01.09.2009
Erschienen in: Journal of Cancer Research and Clinical Oncology / Ausgabe 9/2009
Print ISSN: 0171-5216
Elektronische ISSN: 1432-1335
DOI: https://doi.org/10.1007/s00432-009-0568-6

Neu im Fachgebiet Onkologie

24.04.2024 | DGIM 2024 | Nachrichten

Springer Medizin

A novel role for DYX1C1, a chaperone protein for both Hsp70 and Hsp90, in breast cancer

Abstract

Aims

Main methods

Key findings

Significance

Neu im Fachgebiet Onkologie

Bei Senioren mit Prostatakarzinom auf Anämie achten!

ICI-Therapie in der Schwangerschaft wird gut toleriert

Krebspatienten impfen: Was? Wen? Und wann nicht?

Müde im Alter? Auch an die Nebenniere denken

Update Onkologie

Springer Medizin

Abstract

Aims

Main methods

Key findings

Significance

Bitte loggen Sie sich ein, um Zugang zu diesem Inhalt zu erhalten

Weitere Artikel der Ausgabe 9/2009

Multiplanar MRI–CT fusion neuronavigation-guided serial stereotactic biopsy of human brain tumors: proof of a strong correlation between tumor imaging and histopathology by a new technical approach

Human cervical carcinoma xenograft models for studies of the physiological microenvironment of tumors

Diagnostic accuracy of small breast epithelial mucin mRNA as a marker for bone marrow micrometastasis in breast cancer: a pilot study

Serum levels of nicotinamide N-methyltransferase in patients with lung cancer

Herbal extract “Songyou Yin” inhibits tumor growth and prolongs survival in nude mice bearing human hepatocellular carcinoma xenograft with high metastatic potential

Interdisciplinary S2k guideline on the diagnosis and treatment of cervical carcinoma

Neu im Fachgebiet Onkologie

Bei Senioren mit Prostatakarzinom auf Anämie achten!

ICI-Therapie in der Schwangerschaft wird gut toleriert

Krebspatienten impfen: Was? Wen? Und wann nicht?

Müde im Alter? Auch an die Nebenniere denken

Update Onkologie