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Published in: Journal of Cancer Research and Clinical Oncology 9/2009

01-09-2009 | Original Paper

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

Authors: Yuxin Chen, Muzi Zhao, Saiqun Wang, Jie Chen, Yun Wang, Qinhong Cao, Wenbin Zhou, Jin Liu, Zhiyang Xu, Guoqing Tong, Jianmin Li

Published in: Journal of Cancer Research and Clinical Oncology | Issue 9/2009

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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.
Literature
go back to reference Adamson ED, Mercola D (2002) Egr1 transcription factor: multiple roles in prostate tumor cell growth and survival. Tumour Biol 23(2):93–102PubMedCrossRef Adamson ED, Mercola D (2002) Egr1 transcription factor: multiple roles in prostate tumor cell growth and survival. Tumour Biol 23(2):93–102PubMedCrossRef
go back to reference 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 (2004) “The stress of dying”: the role of heat shock proteins in the regulation of apoptosis. J Cell Sci 117:2641–2651PubMedCrossRef
go back to reference Beere HM, Green DR (2001) Stress management—heat shock protein-70 and the regulation of apoptosis. Trends Cell Biol 11:6–10PubMedCrossRef Beere HM, Green DR (2001) Stress management—heat shock protein-70 and the regulation of apoptosis. Trends Cell Biol 11:6–10PubMedCrossRef
go back to reference 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 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
go back to reference Blatch GL, Lassle M (1999) The tetratricopeptide repeat: a structural motif mediating protein–protein interactions. Bioessays 21:932–939PubMedCrossRef Blatch GL, Lassle M (1999) The tetratricopeptide repeat: a structural motif mediating protein–protein interactions. Bioessays 21:932–939PubMedCrossRef
go back to reference 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 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
go back to reference Calderwood SK, Khaleque MA, Sawyer DB, Ciocca DR (2006) Heat shock proteins in cancer: chaperones of tumorigenesis. Trends Biochem Sci 31:164–172PubMedCrossRef Calderwood SK, Khaleque MA, Sawyer DB, Ciocca DR (2006) Heat shock proteins in cancer: chaperones of tumorigenesis. Trends Biochem Sci 31:164–172PubMedCrossRef
go back to reference 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 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
go back to reference 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 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
go back to reference 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 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
go back to reference 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 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
go back to reference 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 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
go back to reference Freeman BC, Yamamoto KR (2002) Disassembly of transcriptional regulatory complexes by molecular chaperones. Science 296:2232–2235PubMedCrossRef Freeman BC, Yamamoto KR (2002) Disassembly of transcriptional regulatory complexes by molecular chaperones. Science 296:2232–2235PubMedCrossRef
go back to reference 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 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
go back to reference Frydman J, Hohfeld J (1997) Chaperones get in touch: the Hip–Hop connection. Trends Biochem Sci 22:87–92PubMedCrossRef Frydman J, Hohfeld J (1997) Chaperones get in touch: the Hip–Hop connection. Trends Biochem Sci 22:87–92PubMedCrossRef
go back to reference Hartl FU, Hayer-Hartl M (2002) Molecular chaperones in the cytosol: from nascent chain to folded protein. Science 295:1852–1858PubMedCrossRef Hartl FU, Hayer-Hartl M (2002) Molecular chaperones in the cytosol: from nascent chain to folded protein. Science 295:1852–1858PubMedCrossRef
go back to reference 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 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
go back to reference 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, Toft DO (1994) A novel chaperone complex for steroid receptors involving heat shock proteins, immunophilins, and p23. J Biol Chem 269:24989–24993PubMed
go back to reference 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 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
go back to reference 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 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
go back to reference Kaur J, Ralhan R (1995) Differential expression of 70-kDa heat shock-protein in human oral tumorigenesis. Int J Cancer 63:774–779PubMedCrossRef Kaur J, Ralhan R (1995) Differential expression of 70-kDa heat shock-protein in human oral tumorigenesis. Int J Cancer 63:774–779PubMedCrossRef
go back to reference 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 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
go back to reference 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 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
go back to reference Lane DP, Midgley C, Hupp T (1993) Tumour suppressor genes and molecular chaperones. Philos Trans R Soc B 339:369–372 discussion 72–73CrossRef Lane DP, Midgley C, Hupp T (1993) Tumour suppressor genes and molecular chaperones. Philos Trans R Soc B 339:369–372 discussion 72–73CrossRef
go back to reference 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 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
go back to reference 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 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
go back to reference 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 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
go back to reference 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 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
go back to reference Mollerup J, Berchtold MW (2005) The co-chaperone p23 is degraded by caspases and the proteasome during apoptosis. FEBS Lett 579:4187–4192PubMedCrossRef Mollerup J, Berchtold MW (2005) The co-chaperone p23 is degraded by caspases and the proteasome during apoptosis. FEBS Lett 579:4187–4192PubMedCrossRef
go back to reference Neckers L, Neckers K (2002) Heat-shock protein 90 inhibitors as novel cancer chemotherapeutic agents. Expert Opin Emerg Drugs 7:277–288PubMedCrossRef Neckers L, Neckers K (2002) Heat-shock protein 90 inhibitors as novel cancer chemotherapeutic agents. Expert Opin Emerg Drugs 7:277–288PubMedCrossRef
go back to reference 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 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
go back to reference Nollen EA, Morimoto RI (2002) Chaperoning signaling pathways: molecular chaperones as stress-sensing ‘heat shock’ proteins. J Cell Sci 115:2809–2816PubMed Nollen EA, Morimoto RI (2002) Chaperoning signaling pathways: molecular chaperones as stress-sensing ‘heat shock’ proteins. J Cell Sci 115:2809–2816PubMed
go back to reference 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 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
go back to reference 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 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
go back to reference Ramus F (2004) Neurobiology of dyslexia: a reinterpretation of the data. Trends Neurosci 27:720–726PubMedCrossRef Ramus F (2004) Neurobiology of dyslexia: a reinterpretation of the data. Trends Neurosci 27:720–726PubMedCrossRef
go back to reference 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 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
go back to reference 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 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
go back to reference 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 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
go back to reference Steensgaard P, Garre M, Muradore I et al (2004) Sgt1 is required for human kinetochore assembly. EMBO Rep 5:626–631PubMedCrossRef Steensgaard P, Garre M, Muradore I et al (2004) Sgt1 is required for human kinetochore assembly. EMBO Rep 5:626–631PubMedCrossRef
go back to reference 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 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
go back to reference Sullivan WP, Owen BA, Toft DO (2002) The influence of ATP and p23 on the conformation of hsp90. J Biol Chem 277:45942–45948PubMedCrossRef Sullivan WP, Owen BA, Toft DO (2002) The influence of ATP and p23 on the conformation of hsp90. J Biol Chem 277:45942–45948PubMedCrossRef
go back to reference 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 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
go back to reference 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 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
go back to reference 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 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
go back to reference 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 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
go back to reference Wang Y, Paramasivam M, Thomas A et al (2006) DYX1C1 functions in neuronal migration in developing neocortex. Neuroscience 143:515–522PubMedCrossRef Wang Y, Paramasivam M, Thomas A et al (2006) DYX1C1 functions in neuronal migration in developing neocortex. Neuroscience 143:515–522PubMedCrossRef
go back to reference Wong HR, Wispe JR (1997) The stress response and the lung. Am J Physiol 273:L1–L9PubMed Wong HR, Wispe JR (1997) The stress response and the lung. Am J Physiol 273:L1–L9PubMed
go back to reference 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 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
go back to reference 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 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
Metadata
Title
A novel role for DYX1C1, a chaperone protein for both Hsp70 and Hsp90, in breast cancer
Authors
Yuxin Chen
Muzi Zhao
Saiqun Wang
Jie Chen
Yun Wang
Qinhong Cao
Wenbin Zhou
Jin Liu
Zhiyang Xu
Guoqing Tong
Jianmin Li
Publication date
01-09-2009
Publisher
Springer-Verlag
Published in
Journal of Cancer Research and Clinical Oncology / Issue 9/2009
Print ISSN: 0171-5216
Electronic ISSN: 1432-1335
DOI
https://doi.org/10.1007/s00432-009-0568-6

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