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Increased expression of co-chaperone HOP with HSP90 and HSC70 and complex formation in human colonic carcinoma

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Cell Stress and Chaperones Aims and scope

Abstract

Co-chaperone HOP (also called stress-inducible protein 1) is a co-chaperone that interacts with the cytosolic 70-kDa heat shock protein (HSP70) and 90-kDa heat shock protein (HSP90) families using different tetratricopeptide repeat domains. HOP plays crucial roles in the productive folding of substrate proteins by controlling the chaperone activities of HSP70 and HSP90. Here, we examined the levels of HOP, HSC70 (cognate of HSP70, also called HSP73), and HSP90 in the tumor tissues from colon cancer patients, in comparison with the non-tumor tissues from the same patients. Expression level of HOP was significantly increased in the tumor tissues (68% of patients, n = 19). Levels of HSC70 and HSP90 were also increased in the tumor tissues (95% and 74% of patients, respectively), and the HOP level was highly correlated with those of HSP90 (r = 0.77, p < 0.001) and HSC70 (r = 0.68, p < 0.01). Immunoprecipitation experiments indicated that HOP complexes with HSC70 or HSP90 in the tumor tissues. These data are consistent with increased formation of co-chaperone complexes in colon tumor specimens compared to adjacent normal tissue and could reflect a role for HOP in this process.

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Abbreviations

HSP:

heat shock protein

HOP:

HSP70/HSP90 organizing protein

References

  • 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

    CAS  PubMed  Google Scholar 

  • 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 U S A 93:8379–8383

    Article  CAS  PubMed  Google Scholar 

  • Brinker A, Scheufler C, Von Der Mulbe F, Fleckenstein B, Herrmann C, Jung G, Moarefi I, Hartl FU (2002) Ligand discrimination by TPR domains. Relevance and selectivity of EEVD-recognition in Hsp70 × Hop × Hsp90 complexes. J Biol Chem 277:19265–19275

    Article  CAS  PubMed  Google Scholar 

  • Bukau B, Weissman J, Horwich A (2006) Molecular chaperones and protein quality control. Cell 125:443–451

    Article  CAS  PubMed  Google Scholar 

  • Carrigan PE, Riggs DL, Chinkers M, Smith DF (2005) Functional comparison of human and Drosophila Hop reveals novel role in steroid receptor maturation. J Biol Chem 280:8906–8911

    Article  CAS  PubMed  Google Scholar 

  • Chen S, Smith DF (1998) Hop as an adaptor in the heat shock protein 70 (Hsp70) and hsp90 chaperone machinery. J Biol Chem 273:35194–35200

    Article  CAS  PubMed  Google Scholar 

  • Ciocca DR, Calderwood SK (2005) Heat shock proteins in cancer: diagnostic, prognostic, predictive, and treatment implications. Cell Stress Chaperones 10:86–103

    Article  CAS  PubMed  Google Scholar 

  • Csermely P, Schnaider T, Soti C, Prohaszka Z, Nardai G (1998) The 90-kDa molecular chaperone family: structure, function, and clinical applications. A comprehensive review. Pharmacol Ther 79:129–168

    Article  CAS  PubMed  Google Scholar 

  • Fiskus W, Ren Y, Mohapatra A, Bali P, Mandawat A, Rao R, Herger B, Yang Y, Atadja P, Wu J, Bhalla K (2007) Hydroxamic acid analogue histone deacetylase inhibitors attenuate estrogen receptor-alpha levels and transcriptional activity: a result of hyperacetylation and inhibition of chaperone function of heat shock protein 90. Clin Cancer Res 13:4882–4890

    Article  CAS  PubMed  Google Scholar 

  • Grbovic OM, Basso AD, Sawai A, Ye Q, Friedlander P, Solit D, Rosen N (2006) V600E B-Raf requires the Hsp90 chaperone for stability and is degraded in response to Hsp90 inhibitors. Proc Natl Acad Sci USA 103:57–62

    Article  CAS  PubMed  Google Scholar 

  • Isaacs JS, Jung YJ, Mimnaugh EG, Martinez A, Cuttitta F, Neckers LM (2002) Hsp90 regulates a von Hippel Lindau-independent hypoxia-inducible factor-1 alpha-degradative pathway. J Biol Chem 277:29936–29944

    Article  CAS  PubMed  Google Scholar 

  • Ishida R, Takaoka Y, Yamamoto S, Miyazaki T, Otaka M, Watanabe S, Komatsuda A, Wakui H, Sawada K, Kubota H, Itoh H (2008) Cisplatin differently affects amino terminal and carboxyl terminal domains of HSP90. FEBS Lett 582:3879–3883

    Article  CAS  PubMed  Google Scholar 

  • Itoh H, Tashima Y (1990) A novel testis-specific 105-kDa protein related to the 90-kDa heat-shock protein. Eur J Biochem 193:429–435

    Article  CAS  PubMed  Google Scholar 

  • Jiang J, Prasad K, Lafer EM, Sousa R (2005) Structural basis of interdomain communication in the Hsc70 chaperone. Mol Cell 20:513–524

    Article  CAS  PubMed  Google Scholar 

  • Johnson BD, Schumacher RJ, Ross ED, Toft DO (1998) Hop modulates Hsp70/Hsp90 interactions in protein folding. J Biol Chem 273:3679–3686

    Article  CAS  PubMed  Google Scholar 

  • Kamal A, Thao L, Sensintaffar J, Zhang L, Boehm MF, Fritz LC, Burrows FJ (2003) A high-affinity conformation of Hsp90 confers tumour selectivity on Hsp90 inhibitors. Nature 425:407–410

    Article  CAS  PubMed  Google Scholar 

  • Kampinga H, Hageman J, Vos MJ, Kubota H, Tanguay RM, Bruford EA, Cheetham ME, Chen B, Hightower LE (2009) Guidelines for the nomenclature of the human heat shock proteins. Cell Stress Chaperones 14:105–111

    Google Scholar 

  • Miyazaki T, Sagawa R, Honma T, Noguchi S, Harada T, Komatsuda A, Ohtani H, Wakui H, Sawada K, Otaka M, Watanabe S, Jikei M, Ogawa N, Hamada F, Itoh H (2004) 73-kDa molecular chaperone HSP73 is a direct target of antibiotic gentamicin. J Biol Chem 279:17295–17300

    Article  CAS  PubMed  Google Scholar 

  • Muller L, Schaupp A, Walerych D, Wegele H, Buchner J (2004) Hsp90 regulates the activity of wild type p53 under physiological and elevated temperatures. J Biol Chem 279:48846–48854

    Article  PubMed  Google Scholar 

  • Neckers L (2002) Hsp90 inhibitors as novel cancer chemotherapeutic agents. Trends Mol Med 8:S55–61

    Article  CAS  PubMed  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  • Noonan EJ, Place RF, Giardina C, Hightower LE (2007) Hsp70B' regulation and function. Cell Stress Chaperones 12:393–402

    Article  PubMed  Google Scholar 

  • Noonan E, Giardina C, Hightower L (2008) Hsp70B' and Hsp72 form a complex in stressed human colon cells and each contributes to cytoprotection. Exp Cell Res 314:2468–2476

    Article  CAS  PubMed  Google Scholar 

  • Otaka M, Yamamoto S, Ogasawara K, Takaoka Y, Noguchi S, Miyazaki T, Nakai A, Odashima M, Matsuhashi T, Watanabe S, Itoh H (2007) The induction mechanism of the molecular chaperone HSP70 in the gastric mucosa by Geranylgeranylacetone (HSP-inducer). Biochem Biophys Res Commun 353:399–404

    Article  CAS  PubMed  Google Scholar 

  • 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

    CAS  Google Scholar 

  • Richter K, Muschler P, Hainzl O, Reinstein J, Buchner J (2003) Sti1 is a non-competitive inhibitor of the Hsp90 ATPase. Binding prevents the N-terminal dimerization reaction during the atpase cycle. J Biol Chem 278:10328–10333

    Article  CAS  PubMed  Google Scholar 

  • Sato S, Fujita N, Tsuruo T (2000) Modulation of Akt kinase activity by binding to Hsp90. Proc Natl Acad Sci U S A 97:10832–10837

    Article  CAS  PubMed  Google Scholar 

  • 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

    Article  CAS  PubMed  Google Scholar 

  • Schulte TW, Blagosklonny MV, Romanova L, Mushinski JF, Monia BP, Johnston JF, Nguyen P, Trepel J, Neckers LM (1996) Destabilization of Raf-1 by geldanamycin leads to disruption of the Raf-1-MEK-mitogen-activated protein kinase signalling pathway. Mol Cell Biol 16:5839–5845

    CAS  PubMed  Google Scholar 

  • Smith PK, Krohn RI, Hermanson GT, Mallia AK, Gartner FH, Provenzano MD, Fujimoto EK, Goeke NM, Olson BJ, Klenk DC (1985) Measurement of protein using bicinchoninic acid. Anal Biochem 150:76–85

    Article  CAS  PubMed  Google Scholar 

  • Sreedhar AS, Soti C, Csermely P (2004) Inhibition of Hsp90: a new strategy for inhibiting protein kinases. Biochim Biophys Acta 1697:233–242

    CAS  PubMed  Google Scholar 

  • Vaughan CK, Gohlke U, Sobott F, Good VM, Ali MM, Prodromou C, Robinson CV, Saibil HR, Pearl LH (2006) Structure of an Hsp90-Cdc37-Cdk4 complex. Mol Cell 23:697–707

    Article  CAS  PubMed  Google Scholar 

  • Vogel M, Bukau B, Mayer MP (2006) Allosteric regulation of Hsp70 chaperones by a proline switch. Mol Cell 21:359–367

    Article  CAS  PubMed  Google Scholar 

  • Wegele H, Haslbeck M, Reinstein J, Buchner J (2003) Sti1 is a novel activator of the Ssa proteins. J Biol Chem 278:25970–25976

    Article  CAS  PubMed  Google Scholar 

  • Wegele H, Muller L, Buchner J (2004) Hsp70 and Hsp90—a relay team for protein folding. Rev Physiol Biochem Pharmacol 151:1–44

    Article  CAS  PubMed  Google Scholar 

  • Wegele H, Wandinger SK, Schmid AB, Reinstein J, Buchner J (2006) Substrate transfer from the chaperone Hsp70 to Hsp90. J Mol Biol 356:802–811

    Article  CAS  PubMed  Google Scholar 

  • Workman P, Burrows F, Neckers L, Rosen N (2007) Drugging the cancer chaperone HSP90: combinatorial therapeutic exploitation of oncogene addiction and tumor stress. Ann N Y Acad Sci 1113:202–216

    Article  CAS  PubMed  Google Scholar 

  • Yokota S, Yanagi H, Yura T, Kubota H (1999) Cytosolic chaperonin is up-regulated during cell growth. Preferential expression and binding to tubulin at G(1)/S transition through early S phase. J Biol Chem 274:37070–37078

    Article  CAS  PubMed  Google Scholar 

  • Young JC, Agashe VR, Siegers K, Hartl FU (2004) Pathways of chaperone-mediated protein folding in the cytosol. Nat Rev Mol Cell Biol 5:781–791

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

SY was supported by a Sasakawa Scientific Research Grant from the Japan Science Society, and HK was supported by a grant from Suzuken Memorial Foundation.

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Authors and Affiliations

  1. Department of Life Science, Faculty and Graduate School of Engineering and Resource Science, Akita University, 1-1 Tegata-Gakuencho, Akita, 010-8502, Japan

    Hiroshi Kubota, Soh Yamamoto, Eri Itoh, Asami Nakamura, Yukina Izumi, Hirotaka Okada & Hideaki Itoh

  2. Department of Gastroenterological Surgery, Akita University Graduate School of Medicine, Akita, 010-8543, Japan

    Yuki Abe, Masatake Iida & Yuzo Yamamoto

  3. Department of Pathology, Akita University Hospital, Akita, 010-8543, Japan

    Hiroshi Nanjo

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  1. Hiroshi Kubota
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  2. Soh Yamamoto
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Correspondence to Hideaki Itoh.

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Kubota, H., Yamamoto, S., Itoh, E. et al. Increased expression of co-chaperone HOP with HSP90 and HSC70 and complex formation in human colonic carcinoma. Cell Stress and Chaperones 15, 1003–1011 (2010). https://doi.org/10.1007/s12192-010-0211-0

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  • DOI: https://doi.org/10.1007/s12192-010-0211-0

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