Hsp72 and Cell Signalling

doi:10.1017/CBO9780511546310.010

9 - Hsp72 and Cell Signalling

Published online by Cambridge University Press: 10 August 2009

Vladimir L. Gabai and

Michael Y. Sherman

Edited by

Brian Henderson and

A. Graham Pockley

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Vladimir L. Gabai: Affiliation:
Department of Biochemistry, Boston University School of Medicine, Boston, Massachussets, U.S.A.
Michael Y. Sherman: Affiliation:
Department of Biochemistry, Boston University School of Medicine, Boston, Massachussets, U.S.A.
Brian Henderson: Affiliation:
University College London
A. Graham Pockley: Affiliation:
University of Sheffield

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Summary

Introduction

Many signalling molecules such as steroid hormone receptors and other receptors, protein kinases and phosphatases are found associated with various types of heat shock proteins, including Hsp90, Hsp70, Hsp40 and other co-chaperones. The functional role of these associations appears to be multi-faceted and the association of signalling proteins with these chaperone cohorts plays a pivotal role in initial folding and maturation of steroid hormone receptors and many kinases (e.g., Src). In addition, association with Hsp90 and its co-chaperones is critical for the stability of signalling proteins, because inhibition of Hsp90 by geldanamycin and other specific inhibitors leads to rapid ubiquitin-dependent degradation of Raf-1, Akt and other kinases that normally associate with Hsp90 [1, 2]. In fact, the anti-cancer activities of Hsp90 inhibitors could be related to the degradation and downregulation of signalling pathways that are controlled by these kinases [1, 3]. In contrast to Hsp90, which protects from degradation, an association with Hsp70 might target these proteins for rapid ubiquitination (usually via a ubiquitin ligase CHIP) followed by proteolysis [4].

In addition to their critical role in folding, maturation and stability of various signalling components, chaperones may be directly involved in regulation of their activities. In fact, it appears that Hsp70 and other chaperones play a regulatory role in the activation of many signalling pathways that are elicited by heat shock and other stresses.

There are multiple members of the Hsp70 protein family.

Type: Chapter
Information: Molecular Chaperones and Cell Signalling , pp. 144 - 159

DOI: https://doi.org/10.1017/CBO9780511546310.010 [Opens in a new window]

Publisher: Cambridge University Press

Print publication year: 2005

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References

Hostein, I, Robertson, D, DiStefano, F, Workman, P and Andrew Clarke, P. Inhibition of signal transduction by the Hsp90 inhibitor 17-allylamino-17-demethoxygeldanamycin results in cytostasis and apoptosis. Cancer Res 2001, 61: 4003–4009Google Scholar PubMed

Fujita, N, Sato, S, Ishida, A and Tsuruo, T. Involvement of Hsp90 in signaling and stability of 3-phosphoinositide-dependent kinase-1. J Biol Chem 2002, 277: 10346–10353CrossRef Google Scholar PubMed

Neckers, L. Hsp90 inhibitors as novel cancer chemotherapeutic agents. Trends Mol Med 2002, 8: S55–61CrossRef Google Scholar PubMed

Wiederkehr, T, Bukau, B and Buchberger, A. Protein turnover: a CHIP programmed for proteolysis. Cur Biol 2002, 12: R26–28CrossRef Google Scholar PubMed

Michels, A A, Kanon, B, Konings, A W, Ohtsuka, K, Bensaude, O and Kampinga, H H. Hsp70 and Hsp40 chaperone activities in the cytoplasm and the nucleus of mammalian cells. J Biol Chem 1997, 272: 33283–33289CrossRef Google Scholar PubMed

Nollen, E A, Brunsting, J F, Roelofsen, H, Weber, L A and Kampinga, H H. In vivo chaperone activity of heat shock protein 70 and thermotolerance. Mol Cell Biol 1999, 19: 2069–2079CrossRef Google Scholar PubMed

Gabai, V L, Meriin, A B, Mosser, D D, Caron, A W, Rits, S, Shifrin, VI and Sherman, M Y. HSP70 prevent activation of stress kinases: a novel pathway of cellular thermotolerance. J Biol Chem 1997, 272: 18033–18037CrossRef Google Scholar

Mosser, D D, Caron, A W, Bourget, L, Denis-Larose, C and Massie, B. Role of the human heat shock protein hsp70 in protection against stress-induced apoptosis. Mol Cell Biol 1997, 17: 5317–5327CrossRef Google Scholar PubMed

Meriin, A, Gabai, V, Yaglom, J, Shifrin, V and Sherman, M. Proteasome inhibitors activate stress-kinases and induce Hsp72: diverse effects on apoptosis. J Biol Chem 1998, 273: 6373–6379CrossRef Google Scholar PubMed

Hideshima, T, Mitsiades, C, Akiyama, M, Hayashi, T, Chauhan, D, Richardson, P, Schlossman, R, Podar, K, Munshi, N C, Mitsiades, N and Anderson, K C. Molecular mechanisms mediating antimyeloma activity of proteasome inhibitor PS-341. Blood 2003, 101: 1530–1534CrossRef Google Scholar PubMed

Almond, J B and Cohen, G M. The proteasome: a novel target for cancer chemotherapy. Leukemia 2002, 16: 433–443CrossRef Google Scholar PubMed

Yaglom, J A, Gabai, V L, Meriin, A B, Mosser, D D and Sherman, M Y. The function of HSP72 in suppression of c-Jun N-terminal kinase activation can be dissociated from its role in prevention of protein damage. J Biol Chem 1999, 274: 20223–20228CrossRef Google Scholar PubMed

Gabai, V L, Mabuchi, K, Mosser, D D and Sherman, M Y. Hsp72 and stress kinase c-jun N-terminal kinase regulate the bid-dependent pathway in tumor necrosis factor-induced apoptosis. Mol Cell Biol 2002, 22: 3415–3424CrossRef Google Scholar PubMed

Davis, R J. Signal transduction by the JNK group of MAP kinases. Cell 2000, 103: 239–252CrossRef Google Scholar PubMed

Kyriakis, J M a J A. Mammalian mitogen-activated protein kinase signal transduction pathways activated by stress and inflammation. Physiol Rev 2001, 81: 807–869CrossRef Google Scholar PubMed

Su, B and Karin, M. Mitogen-activated protein kinase cascades and regulation of gene expression. Cur Opin Immunol 1996, 8: 402–411CrossRef Google Scholar PubMed

Meriin, A B, Yaglom, J A, Gabai, V L, Mosser, D D, Zon, L and Sherman, M Y. Protein damaging stresses activate JNK via inhibition of its phosphatase: a novel pathway controlled by Hsp72. Mol Cell Biol 1999, 19: 2547–2555CrossRef Google Scholar PubMed

Millward, T A, Zolnierowicz, S and Hemmings, B A. Regulation of protein kinase cascades by protein phosphatase 2A. Trends Biochem Sci 1999, 24: 186–191CrossRef Google Scholar PubMed

Saxena, M and Mustelin, T. Extracellular signals and scores of phosphatases: all roads lead to MAP kinase. Semin Immunol 2000, 12: 387–396CrossRef Google Scholar PubMed

Keyse, S M. Protein phosphatases and the regulation of MAP kinase activity. Semin Cell Develop Biol 1998, 9: 143–152CrossRef Google Scholar PubMed

Keyse, S M. An emerging family of dual specificity MAP kinase phosphatases. Biochim Biophys Acta 1995, 1265: 152–160CrossRef Google Scholar PubMed

Muda, M, Theodosiou, A, Gillieron, C, Smith, A, Chabert, C, Camps, M, Boschert, U, Rodrigues, N, Davies, K, Ashworth, A and Arkinstall, S. The mitogen-activated protein kinase phosphatase-3 N-terminal noncatalytic region is responsible for tight substrate binding and enzymatic specificity. J Biol Chem 1998, 273: 9323–9329CrossRef Google Scholar PubMed

Muda, M, Theodosiou, A, Rodrigues, N, Boschert, U, Camps, M, Gillieron, C, Davies, K, Ashworth, A and Arkinstall, S. The dual specificity phosphatases M3/6 and MKP-3 are highly selective for inactivation of distinct mitogen-activated protein kinases. J Biol Chem 1996, 271: 27205–27208CrossRef Google Scholar PubMed

Todd, J L, Rigas, J D, Rafty, L A and Denu, J M. Dual-specificity protein tyrosine phosphatase VHR down-regulates c-Jun N-terminal kinase (JNK). Oncogene 2002, 21: 2573–2583CrossRef Google Scholar

Chu, Y, Solski, P A, Khosravi-Far, R, Der, C J and Kelly, K. The mitogen-activated protein kinase phosphatases PAC1, MKP-1, and MKP-2 have unique substrate specificities and reduced activity in vivo toward the ERK2 sevenmaker mutation. J Biol Chem 1996, 271: 6497–6501CrossRef Google Scholar PubMed

Palacios, C, Collins, M K and Perkins, G R. The JNK phosphatase M3/6 is inhibited by protein-damaging stress. Cur Biol 2001, 11: 1439–1443CrossRef Google Scholar PubMed

Chen, Y R, Shrivastava, A and Tan, T H. Down-regulation of the c-Jun N-terminal kinase (JNK) phosphatase M3/6 and activation of JNK by hydrogen peroxide and pyrrolidine dithiocarbamate. Oncogene 2001, 20: 367–374CrossRef Google Scholar PubMed

Theodosiou, A and Ashworth, A. Differential effects of stress stimuli on a JNK-inactivating phosphatase. Oncogene 2002, 21: 2387–2397CrossRef Google Scholar PubMed

Merienne, K, Helmlinger, D, Perkin, G R, Devys, D and Trottier, Y. Polyglutamine expansion induces a protein-damaging stress connecting heat shock protein 70 to the JNK pathway. J Biol Chem 2003, 278: 16957–16967CrossRef Google Scholar PubMed

Mosser, D D, Caron, A W, Bourget, L, Meriin, A B, Sherman, M Y, Morimoto, R I and Massie, B. The chaperone function of hsp70 is required for protection against stress-induced apoptosis. Mol Cell Biol 2000, 20: 7146–7159CrossRef Google Scholar PubMed

Park, H-S, Cho, S-G, Kim, C K, Hwang, H S, Noh, K T, Kim, M-S, Huh, S-H, Kim, M J, Ryoo, K, Kim, E K, Kang, W J, Lee, J-S, Seo, J-S, Ko, Y-G, Kim, S and Choi, E-J. Heat shock protein Hsp72 is a negative regulator of apoptosis signal-regulating kinase 1. Mol Cell Biol 2002, 22: 7721–7730CrossRef Google Scholar PubMed

Yaglom, J A, Ekhterae, D, Gabai, V L and Sherman, M Y. Regulation of necrosis of H9C2 myogenic cells upon transient energy deprivation: rapid de-energization of mitochondria precedes necrosis and is controlled by reactive oxygen species, stress-kinase JNK, HSP72 and ARC. J Biol Chem 2003, 278: 50483–50496CrossRef Google Scholar

Song, J, Takeda, M and Morimoto, R I. Bag1-Hsp70 mediates a physiological stress signalling pathway that regulates Raf-1/ERK and cell growth. Nat Cell Biol 2001, 3: 276–282CrossRef Google Scholar PubMed

Bimston, D, Song, J, Winchester, D, Takayama, S, Reed, J C and Morimoto, R I. BAG-1, a negative regulator of Hsp70 chaperone activity, uncouples nucleotide hydrolysis from substrate release. EMBO J 1998, 17: 6871–6878CrossRef Google Scholar PubMed

Park, H S, Lee, J S, Huh, S H, Seo, J S and Choi, E J. Hsp72 functions as a natural inhibitory protein of c-Jun N-terminal kinase. EMBO J 2001, 20: 446–456CrossRef Google Scholar PubMed

Deng, Y, Ren, X, Yang, L, Lin, Y and Wu, X. A JNK-dependent pathway is required for TNFα-induced apoptosis. Cell 2003, 115: 61–70CrossRef Google Scholar PubMed

Beere, H M, Wolf, B B, Cain, K, Mosser, D D, Mahboubi, A, Kuwana, T, Tailor, P, Morimoto, R I, Cohen, G M and Green, D R. Heat-shock protein 70 inhibits apoptosis by preventing recruitment of procaspase-9 to the Apaf-1 apoptosome. Nat Cell Biol 2000, 2: 469–475CrossRef Google Scholar PubMed

Saleh, A, Srinivasula, S, Balkir, L, Robbins, P and Alnemri, E. Negative regulation of the Apaf-1 apoptosome by Hsp70. Nat Cell Biol 2000, 2: 476–483CrossRef Google Scholar PubMed

Proskuryakov, S Y, Konoplyannikov, A G and Gabai, V L. Necrosis: a specific form of programmed cell death?Exp Cell Res 2003, 283: 1–16CrossRef Google Scholar PubMed

Ma, X L, Kumar, S, Gao, F, Louden, C S, Lopez, B L, Christopher, T A, Wang, C, Lee, J C, Feuerstein, G Z and Yue, T L. Inhibition of p38 mitogen-activated protein kinase decreases cardiomyocyte apoptosis and improves cardiac function after myocardial ischemia and reperfusion. Circulation 1999, 99: 1685–1691CrossRef Google Scholar PubMed

Mackay, K and Mochly-Rosen, D. An inhibitor of p38 mitogen-activated protein kinase protects neonatal cardiac myocytes from ischemia. J Biol Chem 1999, 274: 6272–6279CrossRef Google Scholar PubMed

Gabai, V L, Meriin, A B, Yaglom, J A, Wei, J Y, Mosser, D D and Sherman, M Y. Suppression of stress kinase JNK is involved in Hsp72-mediated protection of myogenic cells from transient energy deprivation. Hsp72 alleviates the stress-induced inhibition of JNK dephosphorylation. J Biol Chem 2000, 275: 38088–38094CrossRef Google Scholar PubMed

Uma, S, Thulasiraman, V and Matts, R L. Dual role for Hsc70 in the biogenesis and regulation of the heme-regulated kinase of the alpha subunit of eukaryotic translation initiation factor 2. Mol Cell Biol 1999, 19: 5861–5871CrossRef Google Scholar PubMed

Thulasiraman, V, Xu, Z, Uma, S, Gu, Y, Chen, J J and Matts, R L. Evidence that Hsc70 negatively modulates the activation of the heme-regulated eIF-2 alpha kinase in rabbit reticulocyte lysate. Eur J Biochem 1998, 255: 552–562CrossRef Google Scholar

Chen, J J and London, I M. Regulation of protein synthesis by heme-regulated eIF-2 alpha kinase. Trends Biochem Sci 1995, 20: 105–108CrossRef Google Scholar PubMed

Hinnebusch, A G. The eIF-2 alpha kinases: regulators of protein synthesis in starvation and stress. Semin Cell Biol 1994, 5: 417–426CrossRef Google Scholar

Matts, R L, Xu, Z, Pal, J K and Chen, J J. Interactions of the heme-regulated eIF-2 alpha kinase with heat shock proteins in rabbit reticulocyte lysates. J Biol Chem 1992, 267: 18160–18167Google Scholar PubMed

Matts, R L, Hurst, R and Xu, Z. Denatured proteins inhibit translation in hemin-supplemented rabbit reticulocyte lysate by inducing the activation of the heme-regulated eIF-2 alpha kinase. Biochemistry 1993, 32: 7323–7328CrossRef Google Scholar PubMed

Williams, B R. PKR; a sentinel kinase for cellular stress. Oncogene 1999, 18: 6112–6120CrossRef Google Scholar PubMed

Brostrom, C O, Prostko, C R, Kaufman, R J and Brostrom, M A. Inhibition of translational initiation by activators of the glucose-regulated stress protein and heat shock protein stress response systems. Role of the interferon-inducible double-stranded RNA-activated eukaryotic initiation factor 2 alpha kinase. J Biol Chem 1996, 271: 24995–25002CrossRef Google Scholar

Tang, N M, Ho, C Y and Katze, M G. The 58-kDa cellular inhibitor of the double stranded RNA-dependent protein kinase requires the tetratricopeptide repeat 6 and DnaJ motifs to stimulate protein synthesis in vivo. J Biol Chem 1996, 271: 28660–28666CrossRef Google Scholar PubMed

Melville, M W, Tan, S L, Wambach, M, Song, J, Morimoto, R I and Katze, M G. The cellular inhibitor of the PKR protein kinase, P58(IPK), is an influenza virus-activated co-chaperone that modulates heat shock protein 70 activity. J Biol Chem 1999, 274: 3797–3803CrossRef Google Scholar

Melville, M W, Hansen, W J, Freeman, B C, Welch, W J and Katze, M G. The molecular chaperone hsp40 regulates the activity of P58IPK, the cellular inhibitor of PKR. Proc Nat Acad Sci USA 1997, 94: 97–102CrossRef Google Scholar PubMed

Melville, M W, Katze, M G and Tan, S L. P58IPK, a novel co-chaperone containing tetratricopeptide repeats and a J-domain with oncogenic potential. Cell Mol Life Sci 2000, 57: 311–322CrossRef Google Scholar

Huizen, R, Martindale, J L, Gorospe, M and Holbrook, N J. P58IPK, a novel endoplasmic reticulum stress-inducible protein and potential negative regulator of eIF2 alpha signaling. J Biol Chem 2003, 278: 15558–15564CrossRef Google Scholar

Yan, W, Frank, C L, Korth, M J, Sopher, B L, Novoa, I, Ron, D and Katze, M G. Control of PERK eIF2 alpha kinase activity by the endoplasmic reticulum stress-induced molecular chaperone P58IPK. Proc Nat Acad Sci USA 2002, 99: 15920–15925CrossRef Google Scholar

Ciocca, D R, Clark, G M, Tandon, A K, Fuqua, S A, Welch, W J and McGuire, W L. Heat shock protein hsp70 in patients with axillary lymph node-negative breast cancer: prognostic implications. J Natl Cancer Inst 1993, 85: 570–574CrossRef Google Scholar PubMed

Nanbu, K, Konishi, I, Mandai, M, Kuroda, H, Hamid, A A, Komatsu, T and Mori, T. Prognostic significance of heat shock proteins Hsp70 and Hsp90 In endometrial carcinomas. Cancer Detect Prevent 1998, 22: 549–555CrossRef Google Scholar PubMed

Costa, M J M, Rosas, S L B, Chindano, A, Lima, P D S, Madi, K and Carvalho, M D D. Expression of heat shock protein 70 and P53 in human lung cancer. Oncol Rep 1997, 4: 1113–1116Google Scholar PubMed

Vargasroig, L M, Fanelli, M A, Lopez, L A, Gago, F E, Tello, O, Aznar, J Z and Ciocca, D R. Heat shock proteins and cell proliferation in human breast cancer biopsy samples. Cancer Detect Prevent 1997, 21: 441–451Google Scholar

Hwang, T S, Han, H S, Choi, H K, Lee, Y J, Kim, Y-J, Han, M-Y and Park, Y-M. Differential, stage-dependent expression of Hsp70, Hsp110 and Bcl-2 in colorectal cancer. J Gastroenterol Hepatol 2003, 18: 690–700CrossRef Google Scholar PubMed

Volm, M, Koomagi, R, Mattern, J and Efferth, T. Protein expression profile of primary human squamous cell lung carcinomas indicative of the incidence of metastases. Clin Exp Metastasis 2002, 19: 385–390CrossRef Google Scholar PubMed

Prendergast, G C. Mechanisms of apoptosis by c-Myc. Oncogene 1999, 18: 2967–2987CrossRef Google Scholar PubMed

Nilsson, J A and Cleveland, J L. Myc pathways provoking cell suicide and cancer. Oncogene 2003, 22: 9007–9021CrossRef Google Scholar PubMed

Pelengaris, S, Khan, M and Evan, G I. Suppression of Myc-induced apoptosis in beta cells exposes multiple oncogenic properties of Myc and triggers carcinogenic progression. Cell 2002, 109: 321–334CrossRef Google Scholar PubMed

Pelengaris, S, Khan, M and Evan, G. c-MYC: more than just a matter of life and death. Nat Rev Cancer 2002, 269: 764–776CrossRef Google Scholar

Volloch, V Z and Sherman, M Y. Oncogenic potential of Hsp72. Oncogene 1999, 18: 3648–3651CrossRef Google Scholar PubMed

Jaattela, M. Over-expression of hsp70 confers tumorigenicity to mouse fibrosarcoma cells. Int J Cancer 1995, 60: 689–693CrossRef Google Scholar PubMed

Seo, J S, Park, Y M, Kim, J I, Shim, E H, Kim, C W, Jang, J J, Kim, S H and Lee, W H. T cell lymphoma in transgenic mice expressing the human Hsp70 gene. Biochem Biophys Res Commun 1996, 218: 582–587CrossRef Google Scholar PubMed

Nylandsted, J, Rohde, M, Brand, K, Bastholm, L, Elling, F and Jaattela, M. Selective depletion of heat shock protein 70 (Hsp70) activates a tumor-specific death program that is independent of caspases and bypasses Bcl-2. Proc Natl Acad Sci USA 2000, 97: 7871–7876CrossRef Google Scholar PubMed

Nylandsted, J, Wick, W, Hirt, U A, Brand, K, Rohde, M, Leist, M, Weller, M and Jaattela, M. Eradication of glioblastoma, and breast and colon carcinoma xenografts by Hsp70 depletion. Cancer Res 2002, 62: 7139–7142Google Scholar PubMed

Yaglom, J, O'Callaghan-Sunol, C, Gabai, V and Sherman, M Y. Inactivation of dual-specificity phosphatases is involved in the regulation of extracellular signal-regulated kinases by heat shock and Hsp72. Mol Cell Biol 2003, 23: 3813–3824CrossRef Google Scholar PubMed

Dhillon, A S, Meikle, S, Yazici, Z, Eulitz, M and Kolch, W. Regulation of Raf-1 activation and signalling by dephosphorylation. EMBO J 2002, 21: 64–71CrossRef Google Scholar PubMed

Nylandsted, J, Gyrd-Hansen, M, Danielewicz, A, Fehrenbacher, N, Lademann, U, Hoyer-Hansen, M, Weber, E, Multhoff, G, Rohde, M and Jaattela, M.Heat shock protein 70 promotes cell survival by inhibiting lysosomal membrane permeabilization. J Exp Med 2004, 200: 425–435CrossRef Google Scholar PubMed

Steel, R, Doherty, J P, Buzzard, K, Clemons, N, Hawkins, C J and Anderson, R L.Hsp72 inhibits apoptosis upstream of the mitochondria and not through interactions with Apaf-1. J Biol Chem 2004, 279: 51490–51490CrossRef Google Scholar

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9 - Hsp72 and Cell Signalling

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