Hsp70 protein complexes as drug targets

Current Pharmaceutical Design

Volumn 19, Issue 3, 2013, Pages 404-417

  Assimon, Victoria A ^a   Gillies, Anne T ^a   Rauch, Jennifer N ^a   Gestwicki, Jason E ^a  

^a UNIVERSITY OF MICHIGAN   (United States)

Author keywords

Heat shock protein 70; J proteins; Molecular chaperones; Nucleotide exchange factors; Protein complex; Tetratricopeptide repeat domain containing proteins

Indexed keywords

HEAT SHOCK PROTEIN 70;

AMINO TERMINAL SEQUENCE; BINDING AFFINITY; CARBOXY TERMINAL SEQUENCE; DEGENERATIVE DISEASE; DRUG TARGETING; HIGH THROUGHPUT SCREENING; HUMAN; INFECTION; NEOPLASM; NONHUMAN; PRIORITY JOURNAL; PROTEIN BINDING; PROTEIN INTERACTION; REVIEW; TETRATRICOPEPTIDE REPEAT;

EID: 84876728531     PISSN: 13816128     EISSN: 18734286     Source Type: Journal    
DOI: 10.2174/138161213804143699     Document Type: Review

References (187)

1. Mayer MP, Bukau B. Hsp70 chaperones: cellular functions and molecular mechanism. Cell Mol Life Sci 2005; 62: 670-84.
2. Bukau B, Weissman J, Horwich A. Molecular chaperones and protein quality control. Cell 2006; 125: 443-51.
3. Frydman J. Folding of newly translated proteins in vivo: the role of molecular chaperones. Ann Rev Biochem 2001; 70: 603-47.
4. Hartl FU, Bracher A, Hayer-Hartl M. Molecular chaperones in protein folding and proteostasis. Nature 2011; 475: 324-32.
5. Bercovich B, Stancovski I, Mayer A, et al. Ubiquitin-dependent degradation of certain protein substrates in vitro requires the molecular chaperone Hsc70. J Biol Chem 1997; 272: 9002-10.
6. Arndt V, Rogon C, Hohfeld J. To be, or not to be--molecular chaperones in protein degradation. Cell Mol Life Sci 2007; 64: 2525-41.
7. Kettern N, Dreiseidler M, Tawo R, Hohfeld J. Chaperone-assisted degradation: multiple paths to destruction. Biol Chem 2010; 391: 481-9.
8. Pratt WB, Toft DO. Regulation of signaling protein function and trafficking by the hsp90/hsp70-based chaperone machinery. Exp Biol Med (Maywood) 2003; 228: 111-33.
9. Gamer J, Bujard H, Bukau B. Physical interaction between heat shock proteins DnaK DnaJ, and GrpE and the bacterial heat shock transcription factor sigma 32. Cell 1992; 69: 833-42.
10. Rodriguez F, Arsene-Ploetze F, Rist W, et al. Molecular basis for regulation of the heat shock transcription factor sigma32 by the DnaK and DnaJ chaperones. Mol Cell 2008; 32: 347-58.
11. Tyedmers J, Mogk A, Bukau B. Cellular strategies for controlling protein aggregation. Nat Rev Mol Cell Biol 2010; 11: 777-88.
12. Daugaard M, Rohde M, Jaattela M. The heat shock protein 70 family: Highly homologous proteins with overlapping and distinct functions. FEBS Lett 2007; 581: 3702-10.
13. Brocchieri L, Conway de Macario E, Macario AJ. hsp70 genes in the human genome: Conservation and differentiation patterns predict a wide array of overlapping and specialized functions. BMC Evol Biol 2008; 8: 19.
14. Hohfeld J, Cyr DM, Patterson C. From the cradle to the grave: molecular chaperones that may choose between folding and degradation. EMBO Rep 2001; 2: 885-90.
15. Meimaridou E, Gooljar SB, Chapple JP. From hatching to dispatching: the multiple cellular roles of the Hsp70 molecular chaperone machinery. J Mol Endocrinol 2009; 42: 1-9.
16. Broadley SA, Hartl FU. The role of molecular chaperones in human misfolding diseases. FEBS Lett 2009; 583: 2647-53.
17. Mosser DD, Morimoto RI. Molecular chaperones and the stress of oncogenesis. Oncogene 2004; 23: 2907-18.
18. Otvos L, Rogers ME, et al. Interaction between heat shock proteins and antimicrobial peptides. Biochemistry 2000; 39: 14150-9.
19. Evans CG, Chang L, Gestwicki JE. Heat shock protein 70 (hsp70) as an emerging drug target. J Med Chem 2010; 53: 4585-602.
20. Brodsky JL, Chiosis G. Hsp70 molecular chaperones: emerging roles in human disease and identification of small molecule modulators. Curr Top Med Chem 2006; 6: 1215-25.
21. Patury S, Miyata Y, Gestwicki JE. Pharmacological targeting of the Hsp70 chaperone. Curr Top Med Chem 2009; 9: 1337-51.
22. Gestwicki JE, Marinec PS. Chemical control over protein-protein interactions: beyond inhibitors. Comb Chem High Throughput Screen 2007; 10: 667-75.
23. Berg T. Modulation of protein-protein interactions with small organic molecules. Angew Chem Int Ed Engl 2003; 42: 2462-81.
24. Arkin MR, Wells JA. Small-molecule inhibitors of protein-protein interactions: progressing towards the dream. Nat Rev Drug Discov 2004; 3: 301-17.
25. Bertelsen EB, Chang L, Gestwicki JE, Zuiderweg ER. Solution conformation of wild-type E. coli Hsp70 (DnaK) chaperone complexed with ADP and substrate. Proc Natl Acad Sci 2009; 106: 8471-6.
26. Bork P, Sander C, Valencia A. An ATPase domain common to prokaryotic cell cycle proteins, sugar kinases, actin, and hsp70 heat shock proteins. Proc Natl Acad Sci 1992; 89: 7290-4.
27. Wang H, Kurochkin AV, Pang Y, Hu W, Flynn GC, Zuiderweg ER. NMR solution structure of the 21 kDa chaperone protein DnaK substrate binding domain: a preview of chaperone-protein interaction. Biochemistry 1998; 37: 7929-40.
28. Zhu X, Zhao X, Burkholder WF, et al. Structural analysis of substrate binding by the molecular chaperone DnaK. Science 1996; 272: 1606-14.
29. Young JC, Barral JM, Ulrich Hartl F. More than folding: localized functions of cytosolic chaperones. Trends in biochemical sciences 2003; 28: 541-7.
30. Gaestel M. Molecular chaperones in signal transduction. Handbook of Experimental Pharmacology 2006: 93-109.
31. Mayer MP, Schroder H, Rudiger S, Paal K, Laufen T, Bukau B. Multistep mechanism of substrate binding determines chaperone activity of Hsp70. Nat Struct Biol 2000; 7: 586-93.
32. Vogel M, Mayer MP, Bukau B. Allosteric regulation of Hsp70 chaperones involves a conserved interdomain linker. J Biol Chem 2006; 281: 38705-11.
33. Chang L, Thompson AD, Ung P, Carlson HA, Gestwicki JE. Mutagenesis reveals the complex relationships between ATPase rate and the chaperone activities of Escherichia coli heat shock protein 70 (Hsp70/DnaK). J Biol Chem 2010; 285: 21282-91.
34. Ahmad A, Bhattacharya A, McDonald RA, et al. Heat shock protein 70 kDa chaperone/DnaJ cochaperone complex employs an unusual dynamic interface. Proc Natl Acad Sci 2011; 108: 18966-71.
35. Sondermann H, Scheufler C, Schneider C, Hohfeld J, Hartl FU, Moarefi I. Structure of a Bag/Hsc70 complex: convergent functional evolution of Hsp70 nucleotide exchange factors. Science 2001; 291: 1553-7.
36. Liu FH, Wu SJ, Hu SM, Hsiao CD, Wang C. Specific interaction of the 70-kDa heat shock cognate protein with the tetratricopeptide repeats. J Biol Chem 1999; 274: 34425-32.
37. Whitesell L, Lindquist SL. HSP90 and the chaperoning of cancer. Nat Rev Cancer 2005; 5: 761-72.
38. Allan RK, Ratajczak T. Versatile TPR domains accommodate different modes of target protein recognition and function. Cell Stress & Chaperones 2011; 16: 353-67.
39. Borges JC, Ramos CHI. Spectroscopic and thermodynamic measurements of nucleotide-induced changes in the human 70-kDa heat shock cognate protein. Arch Biochem Biophys 2006; 452: 46-54.
40. Williamson DS, Borgognoni J, Clay A, et al. Novel Adenosine-Derived Inhibitors of 70 kDa Heat Shock Protein, Discovered Through Structure-Based Design. J Med Chem 2009; 52: 1510-3.
41. Massey AJ. ATPases as drug targets: insights from heat shock proteins 70 and 90. J Med Chem 2010; 53: 7280-6.
42. Massey AJ, Williamson DS, Browne H, et al. A novel, small molecule inhibitor of Hsc70/Hsp70 potentiates Hsp90 inhibitor induced apoptosis in HCT116 colon carcinoma cells. Cancer Chemother Pharmacol 2011; 66: 535-45.
43. Macias AT, Williamson DS, Allen N, et al. Adenosine-derived inhibitors of 78 kDa glucose regulated protein (Grp78) ATPase: insights into isoform selectivity. J Med Chem 2010; 54: 4034-41.
44. Kragol G, Lovas S, Varadi G, Condie BA, Hoffmann R, Otvos L. The antibacterial peptide pyrrhocoricin inhibits the ATPase actions of DnaK and prevents chaperone-assisted protein folding. Biochemistry 2001; 40: 3016-26.
45. Rerole AL, Gobbo J, De Thonel A, et al. Peptides and aptamers targeting HSP70: a novel approach for anticancer chemotherapy. Cancer Res 2011; 71: 484-95.
46. Rerole AL, Jego G, Garrido C. Hsp70: anti-apoptotic and tumorigenic protein. Methods Mol Biol 2011; 787: 205-30.
47. Williams DR, Ko SK, Park S, Lee MR, Shin I. An apoptosisinducing small molecule that binds to heat shock protein 70. Angew Chem Int Ed Engl 2008; 47: 7466-9.
48. Jinwal UK, Miyata Y, Koren J, 3rd, et al. Chemical manipulation of hsp70 ATPase activity regulates tau stability. J Neurosci 2009; 29: 12079-88.
49. Cellitti J, Zhang Z, Wang S, et al. Small molecule DnaK modulators targeting the beta-domain. Chem Biol Drug Des 2009; 74: 349-57.
50. Qiu XB, Shao YM, Miao S, Wang L. The diversity of the DnaJ/Hsp40 family, the crucial partners for Hsp70 chaperones. Cell Mol Life Sci 2006; 63: 2560-70.
51. Kampinga HH, Hageman J, Vos MJ, et al. Guidelines for the nomenclature of the human heat shock proteins. Cell Stress Chaperones 2009; 14: 105-11.
52. Caplan AJ, Cyr DM, Douglas MG. YDJ1p facilitates polypeptide translocation across different intracellular membranes by a conserved mechanism. Cell 1992; 71: 1143-55.
53. Hageman J, van Waarde MA, Zylicz A, Walerych D, Kampinga HH. The diverse members of the mammalian HSP70 machine show distinct chaperone-like activities. Biochem J 2011; 435: 127-42.
54. Sterrenberg JN, Blatch GL, Edkins AL. Human DNAJ in cancer and stem cells. Cancer Lett 2011; 312: 129-42.
55. Kalia SK, Kalia LV, McLean PJ. Molecular chaperones as rational drug targets for Parkinson's disease therapeutics. CNS Neurol Disord Drug Targets 2010; 9: 741-53.
56. Mitra A, Shevde LA, Samant RS. Multi-faceted role of HSP40 in cancer. Clin Exp Metastasis 2009; 26: 559-67.
57. Harms MB, Sommerville RB, Allred P, et al. Exome sequencing reveals DNAJB6 mutations in dominantly-inherited myopathy. Ann Neurol 2012; 71: 407-16.
58. Knox C, Luke GA, Blatch GL, Pesce ER. Heat shock protein 40 (Hsp40) plays a key role in the virus life cycle. Virus Res 2011; 160: 15-24.
59. Langer T, Lu C, Echols H, Flanagan J, Hayer MK, Hartl FU. Successive action of DnaK, DnaJ and GroEL along the pathway of chaperone-mediated protein folding. Nature 1992; 356: 683-9.
60. Wall D, Zylicz M, Georgopoulos C. The conserved G/F motif of the DnaJ chaperone is necessary for the activation of the substrate binding properties of the DnaK chaperone. J Biol Chem 1995; 270: 2139-44.
61. Szabo A, Langer T, Schroder H, Flanagan J, Bukau B, Hartl FU. The ATP hydrolysis-dependent reaction cycle of the Escherichia coli Hsp70 system DnaK, DnaJ, and GrpE. Proc Natl Acad Sci USA 1994; 91: 10345-9.
62. Greene MK, Maskos K, Landry SJ. Role of the J-domain in the cooperation of Hsp40 with Hsp70. Proc Natl Acad Sci USA 1998; 95: 6108-13.
63. Gassler CS, Buchberger A, Laufen T, et al. Mutations in the DnaK chaperone affecting interaction with the DnaJ cochaperone. Proc Natl Acad Sci USA 1998; 95: 15229-34.
64. Suh WC, Burkholder WF, Lu CZ, Zhao X, Gottesman ME, Gross CA. Interaction of the Hsp70 molecular chaperone, DnaK, with its cochaperone DnaJ. Proc Natl Acad Sci USA 1998; 95: 15223-8.
65. Hennessy F, Nicoll WS, Zimmermann R, Cheetham ME, Blatch GL. Not all J domains are created equal: implications for the specificity of Hsp40-Hsp70 interactions. Protein Sci 2005; 14: 1697-709.
66. Awad W, Estrada I, Shen Y, Hendershot LM. BiP mutants that are unable to interact with endoplasmic reticulum DnaJ proteins provide insights into interdomain interactions in BiP. Proc Natl Acad Sci USA 2008; 105: 1164-9.
67. Vembar SS, Jonikas MC, Hendershot LM, Weissman JS, Brodsky JL. J domain co-chaperone specificity defines the role of BiP during protein translocation. J Biol Chem 2010; 285: 22484-94.
68. Cheetham ME, Caplan AJ. Structure, function and evolution of DnaJ: conservation and adaptation of chaperone function. Cell Stress Chaperones 1998; 3: 28-36.
69. Kampinga HH, Craig EA. The HSP70 chaperone machinery: J proteins as drivers of functional specificity. Nat Rev Mol Cell Biol 2010; 11: 579-92.
70. Holstein SE, Ungewickell H, Ungewickell E. Mechanism of clathrin basket dissociation: separate functions of protein domains of the DnaJ homologue auxilin. J Cell Biol 1996; 135: 925-37.
71. Xing Y, Bocking T, Wolf M, Grigorieff N, Kirchhausen T, Harrison SC. Structure of clathrin coat with bound Hsc70 and auxilin: mechanism of Hsc70-facilitated disassembly. EMBO J 2010; 29: 655-65.
72. Bocking T, Aguet F, Harrison SC, Kirchhausen T. Single-molecule analysis of a molecular disassemblase reveals the mechanism of Hsc70-driven clathrin uncoating. Nat Struct Mol Biol 2011; 18: 295-301.
73. Wang AM, Morishima Y, Clapp KM, et al. Inhibition of hsp70 by methylene blue affects signaling protein function and ubiquitination and modulates polyglutamine protein degradation. J Biol Chem 2010; 285: 15714-23.
74. Nakanishi K, Kamiguchi K, Torigoe T, et al. Localization and function in endoplasmic reticulum stress tolerance of ERdj3, a new member of Hsp40 family protein. Cell Stress Chaperones 2004; 9: 253-64.
75. Shen Y, Hendershot LM. ERdj3, a stress-inducible endoplasmic reticulum DnaJ homologue, serves as a cofactor for BiP's interactions with unfolded substrates. Mol Biol Cell 2005; 16: 40-50.
76. Fan CY, Lee S, Ren HY, Cyr DM. Exchangeable chaperone modules contribute to specification of type I and type II Hsp40 cellular function. Mol Biol Cell 2004; 15: 761-73.
77. Lu Z, Cyr DM. The conserved carboxyl terminus and zinc fingerlike domain of the co-chaperone Ydj1 assist Hsp70 in protein folding. J Biol Chem 1998; 273: 5970-8.
78. Lee S, Fan CY, Younger JM, Ren H, Cyr DM. Identification of essential residues in the type II Hsp40 Sis1 that function in polypeptide binding. J Biol Chem 2002; 277: 21675-82.
79. Rudiger S, Schneider-Mergener J, Bukau B. Its substrate specificity characterizes the DnaJ co-chaperone as a scanning factor for the DnaK chaperone. EMBO J 2001; 20: 1042-50.
80. Feifel B, Schonfeld HJ, Christen P. D-peptide ligands for the cochaperone DnaJ. J Biol Chem 1998; 273: 11999-2002.
81. Li J, Qian X, Sha B. The crystal structure of the yeast Hsp40 Ydj1 complexed with its peptide substrate. Structure 2003; 11: 1475-83.
82. Arawaka S, Machiya Y, Kato T. Heat shock proteins as suppressors of accumulation of toxic prefibrillar intermediates and misfolded proteins in neurodegenerative diseases. Curr Pharm Biotechnol 2010; 11: 158-66.
83. Jana NR, Tanaka M, Wang G, Nukina N. Polyglutamine lengthdependent interaction of Hsp40 and Hsp70 family chaperones with truncated N-terminal huntingtin: their role in suppression of aggregation and cellular toxicity. Hum Mol Genet 2000; 9: 2009-18.
84. Zhou H, Li SH, Li XJ. Chaperone suppression of cellular toxicity of huntingtin is independent of polyglutamine aggregation. J Biol Chem 2001; 276: 48417-24.
85. Chuang JZ, Zhou H, Zhu M, Li SH, Li XJ, Sung CH. Characterization of a brain-enriched chaperone, MRJ, that inhibits Huntingtin aggregation and toxicity independently. J Biol Chem 2002; 277: 19831-8.
86. Hay DG, Sathasivam K, Tobaben S, et al. Progressive decrease in chaperone protein levels in a mouse model of Huntington's disease and induction of stress proteins as a therapeutic approach. Hum Mol Genet 2004; 13: 1389-405.
87. Wyttenbach A, Carmichael J, Swartz J, et al. Effects of heat shock, heat shock protein 40 (HDJ-2), and proteasome inhibition on protein aggregation in cellular models of Huntington's disease. Proc Natl Acad Sci USA 2000; 97: 2898-903.
88. Miyata Y, Koren J, Kiray J, Dickey CA, Gestwicki JE. Molecular chaperones and regulation of tau quality control: strategies for drug discovery in tauopathies. Future Med Chem 2011; 3: 1523-37.
89. Sahara N, Maeda S, Yoshiike Y, et al. Molecular chaperonemediated tau protein metabolism counteracts the formation of granular tau oligomers in human brain. J Neurosci Res 2007; 85: 3098-108.
90. Abisambra JF, Jinwal UK, Suntharalingam A, et al. DnaJA1 Antagonizes Constitutive Hsp70-Mediated Stabilization of Tau. J Mol Biol 2012.
91. Nadler SG, Tepper MA, Schacter B, Mazzucco CE. Interaction of the immunosuppressant deoxyspergualin with a member of the Hsp70 family of heat shock proteins. Science 1992; 258: 484-6.
92. Brodsky JL. Selectivity of the molecular chaperone-specific immunosuppressive agent 15-deoxyspergualin: modulation of Hsc70 ATPase activity without compromising DnaJ chaperone interactions. Biochem Pharmacol 1999; 57: 877-80.
93. Nadeau K, Nadler SG, Saulnier M, Tepper MA, Walsh CT. Quantitation of the interaction of the immunosuppressant deoxyspergualin and analogs with Hsc70 and Hsp90. Biochemistry 1994; 33: 2561-7.
94. Fewell SW, Day BW, Brodsky JL. Identification of an inhibitor of hsc70-mediated protein translocation and ATP hydrolysis. J Biol Chem 2001; 276: 910-4.
95. Mamelak D, Mylvaganam M, Whetstone H, et al. Hsp70s contain a specific sulfogalactolipid binding site. Differential aglycone influence on sulfogalactosyl ceramide binding by recombinant prokaryotic and eukaryotic hsp70 family members. Biochemistry 2001; 40: 3572-82.
96. Mamelak D, Lingwood C. The ATPase domain of hsp70 possesses a unique binding specificity for 3'-sulfogalactolipids. J Biol Chem 2001; 276: 449-56.
97. Park HJ, Mylvaganum M, McPherson A, Fewell SW, Brodsky JL, Lingwood CA. A soluble sulfogalactosyl ceramide mimic promotes Delta F508 CFTR escape from endoplasmic reticulum associated degradation. Chem Biol 2009; 16: 461-70.
98. Fewell SW, Smith CM, Lyon MA, et al. Small molecule modulators of endogenous and co-chaperone-stimulated Hsp70 ATPase activity. J Biol Chem 2004; 279: 51131-40.
99. Wisen S, Bertelsen EB, Thompson AD, et al. Binding of a small molecule at a protein-protein interface regulates the chaperone activity of hsp70-hsp40. ACS Chem Biol 2010; 5: 611-22.
100. Chang L, Bertelsen EB, Wisen S, et al. High-throughput screen for small molecules that modulate the ATPase activity of the molecular chaperone DnaK. Anal Biochem 2008; 372: 167-76.
101. Wisen S, Androsavich J, Evans CG, Chang L, Gestwicki JE. Chemical modulators of heat shock protein 70 (Hsp70) by sequential, microwave-accelerated reactions on solid phase. Bioorg Med Chem Lett 2008; 18: 60-5.
102. Braunstein MJ, Scott SS, Scott CM, et al. Antimyeloma Effects of the Heat Shock Protein 70 Molecular Chaperone Inhibitor MAL3-101. J Oncol 2011; 2011: 232037.
103. Walter GM, Smith MC, Wisen S, et al. Ordered assembly of heat shock proteins, Hsp26, Hsp70, Hsp90, and Hsp104, on expanded polyglutamine fragments revealed by chemical probes. J Biol Chem 2011; 286: 40486-93.
104. Koren J, 3rd, Jinwal UK, Jin Y, et al. Facilitating Akt clearance via manipulation of Hsp70 activity and levels. J Biol Chem 2010; 285: 2498-505.
105. Chang L, Miyata Y, Ung PM, et al. Chemical screens against a reconstituted multiprotein complex: myricetin blocks DnaJ regulation of DnaK through an allosteric mechanism. Chem Biol 2011; 18: 210-21.
106. Congdon EE, Wu JW, Myeku N, et al. Methylthioninium chloride (methylene blue) induces autophagy and attenuates tauopathy in vitro and in vivo. Autophagy 2012; 8.
107. O'Leary JC, 3rd, Li Q, et al. Phenothiazine-mediated rescue of cognition in tau transgenic mice requires neuroprotection and reduced soluble tau burden. Mol Neurodegener 2010; 5: 45.
108. Miyata Y, Chang L, Bainor A, et al. High-throughput screen for Escherichia coli heat shock protein 70 (Hsp70/DnaK): ATPase assay in low volume by exploiting energy transfer. J Biomol Screen 2010; 15: 1211-9.
109. Seguin SP, Evans CW, Nebane-Akah M, et al. High-throughput screening identifies a bisphenol inhibitor of SV40 large T antigen ATPase activity. J Biomol Screen 2012; 17: 194-203.
110. Harrison C. GrpE, a nucleotide exchange factor for DnaK. Cell Stress & Chaperones 2003; 8: 218-24.
111. Carrettiero DC, Hernandez I, Neveu P, Papagiannakopoulos T, Kosik KS. The cochaperone BAG2 sweeps paired helical filamentinsoluble tau from the microtubule. J Neurosci 2009; 29: 2151-61.
112. Elliott E, Tsvetkov P, Ginzburg I. BAG-1 associates with Hsc70. Tau complex and regulates the proteasomal degradation of Tau protein. J Biol Chem 2007; 282: 37276-84.
113. Souza AP, Albuquerque C, Torronteguy C, et al. HspBP1 levels are elevated in breast tumor tissue and inversely related to tumor aggressiveness. Cell Stress & Chaperones 2009; 14: 301-10.
114. Elliott E, Laufer O, Ginzburg I. BAG-1M is up-regulated in hippocampus of Alzheimer's disease patients and associates with tau and APP proteins. J Neurochem 2009; 109: 1168-78.
115. Knoll R, Hoshijima M, Hoffman HM, et al. The cardiac mechanical stretch sensor machinery involves a Z disc complex that is defective in a subset of human dilated cardiomyopathy. Cell 2002; 111: 943-55.
116. Nakamura J, Fujimoto M, Yasuda K, et al. Targeted disruption of Hsp110/105 gene protects against ischemic stress. Stroke 2008; 39: 2853-9.
117. Subjeck JR, Sciandra JJ, Chao CF, Johnson RJ. Heat shock proteins and biological response to hyperthermia. British J Cancer. Supplement 1982; 5: 127-31.
118. Ishihara K, Yasuda K, Hatayama T. Molecular cloning, expression and localization of human 105 kDa heat shock protein, hsp105. Biochim Biophys Acta 1999; 1444: 138-42.
119. Dorard C, de Thonel A, Collura A, et al. Expression of a mutant HSP110 sensitizes colorectal cancer cells to chemotherapy and improves disease prognosis. Nat Med 2011; 17: 1283-9.
120. Hosaka S, Nakatsura T, Tsukamoto H, Hatayama T, Baba H, Nishimura Y. Synthetic small interfering RNA targeting heat shock protein 105 induces apoptosis of various cancer cells both in vitro and in vivo. Cancer Sci 2006; 97: 623-32.
121. Liu Q, Hendrickson WA. Insights into Hsp70 chaperone activity from a crystal structure of the yeast Hsp110 Sse1. Cell 2007; 131: 106-20.
122. Oh HJ, Easton D, Murawski M, Kaneko Y, Subjeck JR. The chaperoning activity of hsp110. Identification of functional domains by use of targeted deletions. J Biol Chem 1999; 274: 15712-8.
123. Dragovic Z, Broadley SA, Shomura Y, Bracher A, Hartl FU. Molecular chaperones of the Hsp110 family act as nucleotide exchange factors of Hsp70s. EMBO J 2006; 25: 2519-28.
124. Goeckeler JL, Stephens A, Lee P, Caplan AJ, Brodsky JL. Overexpression of yeast Hsp110 homolog Sse1p suppresses ydj1-151 thermosensitivity and restores Hsp90-dependent activity. Mol Biol Celll 2002; 13: 2760-70.
125. Oh HJ, Chen X, Subjeck JR. Hsp110 protects heat-denatured proteins and confers cellular thermoresistance. J Biol Chemy 1997; 272: 31636-40.
126. Yamagishi N, Yokota M, Yasuda K, Saito Y, Nagata K, Hatayama T. Characterization of stress sensitivity and chaperone activity of Hsp105 in mammalian cells. Biochem Biophys Res Commun 2011; 409: 90-5.
127. Shaner L, Trott A, Goeckeler JL, Brodsky JL, Morano KA. The function of the yeast molecular chaperone Sse1 is mechanistically distinct from the closely related hsp70 family. J Biol Chem 2004; 279: 21992-2001.
128. Schuermann JP, Jiang J, Cuellar J, et al. Structure of the Hsp110:Hsc70 nucleotide exchange machine. Mol Cell 2008; 31: 232-43.
129. Polier S, Dragovic Z, Hartl FU, Bracher A. Structural basis for the cooperation of Hsp70 and Hsp110 chaperones in protein folding. Cell 2008; 133: 1068-79.
130. Hendrickson WA, Liu Q. Exchange we can believe in. Structure 2008; 16: 1153-5.
131. Wilson CG, Arkin MR. Small-molecule inhibitors of IL-2/IL-2R: lessons learned and applied. Current Topics Microbiol. Immunol 2011; 348: 25-59.
132. DeLano WL, Ultsch MH, de Vos AM, Wells JA. Convergent solutions to binding at a protein-protein interface. Science 2000; 287: 1279-83.
133. Wells JA, McClendon CL. Reaching for high-hanging fruit in drug discovery at protein-protein interfaces. Nature 2007; 450: 1001-9.
134. McLellan CA, Raynes DA, Guerriero V. HspBP1, an Hsp70 cochaperone, has two structural domains and is capable of altering the conformation of the Hsp70 ATPase domain. J Biol Chem 2003; 278: 19017-22.
135. Shomura Y, Dragovic Z, Chang HC, et al. Regulation of Hsp70 function by HspBP1: structural analysis reveals an alternate mechanism for Hsp70 nucleotide exchange. Mol Cell 2005; 17: 367-79.
136. Tanimura S, Hirano AI, Hashizume J, et al. Anticancer drugs upregulate HspBP1 and thereby antagonize the prosurvival function of Hsp70 in tumor cells. J Biol Chem 2007; 282: 35430-9.
137. Takayama S, Xie Z, Reed JC. An evolutionarily conserved family of Hsp70/Hsc70 molecular chaperone regulators. J Biol Chem 1999; 274: 781-6.
138. Takayama S, Bimston DN, Matsuzawa S, et al. BAG-1 modulates the chaperone activity of Hsp70/Hsc70. EMBO J 1997; 16: 4887-96.
139. Briknarova K, Takayama S, Brive L, et al. Structural analysis of BAG1 cochaperone and its interactions with Hsc70 heat shock protein. Nat Struct Biol 2001; 8: 349-52.
140. Takayama S, Sato T, Krajewski S, et al. Cloning and functional analysis of BAG-1: a novel Bcl-2-binding protein with anti-cell death activity. Cell 1995; 80: 279-84.
141. Zeiner M, Gehring U. A protein that interacts with members of the nuclear hormone receptor family: identification and cDNA cloning. Proc Natl Acad Sci 1995; 92: 11465-9.
142. Yang X, Chernenko G, Hao Y, et al. Human BAG-1/RAP46 protein is generated as four isoforms by alternative translation initiation and overexpressed in cancer cells. Oncogene 1998; 17: 981-9.
143. Townsend PA, Cutress RI, Sharp A, Brimmell M, Packham G. BAG-1: a multifunctional regulator of cell growth and survival. Biochim Biophys Acta 2003; 1603: 83-98.
144. Gehring U. Multiple, but concerted cellular activities of the human protein Hap46/BAG-1M and isoforms. Int. J Mol Sci 2009; 10: 906-28.
145. Luders J, Demand J, Hohfeld J. The ubiquitin-related BAG-1 provides a link between the molecular chaperones Hsc70/Hsp70 and the proteasome. J Biol Chemy 2000; 275: 4613-7.
146. Tsukahara F, Maru Y. Bag1 directly routes immature BCR-ABL for proteasomal degradation. Blood 2010; 116: 3582-92.
147. Sroka K, Voigt A, Deeg S, et al. BAG1 modulates huntingtin toxicity, aggregation, degradation, and subcellular distribution. J Neurochem 2009; 111: 801-7.
148. Sharp A, Crabb SJ, Johnson PW, et al. Thioflavin S (NSC71948) interferes with Bcl-2-associated athanogene (BAG-1)-mediated protein-protein interactions. J Pharm Exp Med 2009; 331: 680-9.
149. Leu JI, Pimkina J, Frank A, Murphy ME, George DL. A small molecule inhibitor of inducible heat shock protein 70. Mol Cell 2009; 36: 15-27.
150. Xu Z, Page RC, Gomes MM, et al. Structural basis of nucleotide exchange and client binding by the Hsp70 cochaperone Bag2. Nat Struct Mol Biol 2008; 15: 1309-17.
151. Arndt V, Daniel C, Nastainczyk W, Alberti S, Hohfeld J. BAG-2 acts as an inhibitor of the chaperone-associated ubiquitin ligase CHIP. Mol Biol Cell 2005; 16: 5891-900.
152. Franceschelli S, Rosati A, Lerose R, De Nicola S, Turco MC, Pascale M. Bag3 gene expression is regulated by heat shock factor 1. J Cell Physiol 2008; 215: 575-7.
153. Dai C, Whitesell L, Rogers AB, Lindquist S. Heat shock factor 1 is a powerful multifaceted modifier of carcinogenesis. Cell 2007; 130: 1005-18.
154. Chiappetta G, Ammirante M, Basile A, et al. The antiapoptotic protein BAG3 is expressed in thyroid carcinomas and modulates apoptosis mediated by tumor necrosis factor-related apoptosisinducing ligand. J Clin Endocrinol Metabolism 2007; 92: 1159-63.
155. Jacobs AT, Marnett LJ. HSF1-mediated BAG3 expression attenuates apoptosis in 4-hydroxynonenal-treated colon cancer cells via stabilization of anti-apoptotic Bcl-2 proteins. J Biol Chem 2009; 284: 9176-83.
156. Wang HQ, Liu BQ, Gao YY, et al. Inhibition of the JNK signalling pathway enhances proteasome inhibitor-induced apoptosis of kidney cancer cells by suppression of BAG3 expression. British J Pharmacol 2009; 158: 1405-12.
157. Festa M, Del Valle L, Khalili K, et al. BAG3 protein is overexpressed in human glioblastoma and is a potential target for therapy. Am J Path 2011; 178: 2504-12.
158. Liu P, Xu B, Li J, Lu H. BAG3 gene silencing sensitizes leukemic cells to Bortezomib-induced apoptosis. FEBS letters 2009; 583: 401-6.
159. Goebl M, Yanagida M. The TPR Snap Helix-a novel protein repeat motif from mitosis to transcription. Trends Biochem Sci 1991; 16: 173-7.
160. Lamb JR, Tugendreich S, Hieter P. Tetratrico peptide repeat interactions: to TPR or not to TPR? Trends Biochem Sci 1995; 20: 257-9.
161. Blatch GL, Lässle M, Zetter BR, Kundra V. Isolation of a mouse cDNA encoding mSTI1, a stress-inducible protein containing the TPR motif. Gene 1997; 194: 277-82.
162. D'Andrea LD, Regan L. TPR proteins: the versatile helix. Trends Biochem Sci 2003; 28: 655-62.
163. Sikorski RS, Boguski MS, Goebl M, Hieter P. A repeating amino acid motif in CDC23 defines a family of proteins and a new relationship among genes required for mitosis and RNA synthesis. Cell 1990; 60: 307-17.
164. Hirano T, Kinoshita N, Morikawa K, Yanagida M. Snap helix with knob and hole: Essential repeats in S. pombe nuclear protein nuc2 +. Cell 1990; 60: 319-28.
165. Zhang M, Windheim M, Roe SM, et al. Chaperoned ubiquitylation--crystal structures of the CHIP U box E3 ubiquitin ligase and a CHIP-Ubc13-Uev1a complex. Mol Cell 2005; 20: 525-38.
166. Connell P, Ballinger CA, Jiang J, et al. The co-chaperone CHIP regulates protein triage decisions mediated by heat-shock proteins. Nat Cell Biol 2001; 3: 93-6.
167. Qian SB, McDonough H, Boellmann F, Cyr DM, Patterson C. CHIP-mediated stress recovery by sequential ubiquitination of substrates and Hsp70. Nature 2006; 440: 551-5.
168. Scheufler C, Brinker A, Bourenkov G, et al. Structure of TPR domain-peptide complexes: Critical elements in the assembly of the Hsp70-Hsp90 multichaperone machine. Cell 2000; 101: 199-210.
169. Brinker A, Scheufler C, von der Mulbe F, et al. Ligand discrimination by TPR domains-Relevance and selectivity of EEVD-recognition in Hsp70 center dot Hop center dot Hsp90 complexes. J Biol Chem 2002; 277: 19265-75.
170. Chen S, Smith DF. Hop as an adaptor in the heat shock protein 70 (Hsp70) and hsp90 chaperone machinery. J Biol Chem 1998; 273: 35194-200.
171. Morishima Y, Murphy PJ, Li DP, Sanchez ER, Pratt WB. Stepwise assembly of a glucocorticoid receptor. hsp90 heterocomplex resolves two sequential ATP-dependent events involving first hsp70 and then hsp90 in opening of the steroid binding pocket. J Biol Chem 2000; 275: 18054-60.
172. Hutchison KA, Dittmar KD, Czar MJ, Pratt WB. Proof that hsp70 is required for assembly of the glucocorticoid receptor into a heterocomplex with hsp90. J Biol Chem 1994; 269: 5043-9.
173. Smith DF. Dynamics of heat shock protein 90-progesterone receptor binding and the disactivation loop model for steroid receptor complexes. Mol Endocrinol 1993; 7: 1418-29.
174. Young JC, Barral JM, Hartl FU. More than folding: localized functions of cytosolic chaperones. Trends Biochem Sci 2003; 28: 541-7.
175. Meimaridou E, Gooljar SB, Chapple JP. From hatching to dispatching: the multiple cellular roles of the Hsp70 molecular chaperone machinery. J Mol Endocrinol 2009; 42: 1-9.
176. Hohfeld J, Cyr DM, Patterson C. From the cradle to the grave: molecular chaperones that may choose between folding and degradation. EMBO Reports 2001; 2: 885-90.
177. Wu SJ, Liu FH, Hu SM, Wang C. Different combinations of the heat-shock cognate protein 70 (hsc70) C-terminal functional groups are utilized to interact with distinct tetratricopeptide repeatcontaining proteins. Biochem. J. 2001; 359: 419-26.
178. Ballinger CA, Connell P, Wu YX, et al. Identification of CHIP, a novel tetratricopeptide repeat-containing protein that interacts with heat shock proteins and negatively regulates chaperone functions. Mol Cell Biol 1999; 19: 4535-45.
179. Wang L, Liu YT, Hao R, et al. Molecular Mechanism of the Negative Regulation of Smad1/5 Protein by Carboxyl Terminus of Hsc70-interacting Protein (CHIP). J Biol Chem 2011; 286.
180. Liu FH, Wu SJ, Hu SM, Hsiao CD, Wang C. Specific interaction of the 70-kDa heat shock cognate protein with the tetratricopeptide repeats. J Biol Chem 1999; 274: 34425-32.
181. Carrigan PE, Nelson GM, Roberts PJ, Stoffer JN, Riggs DL, Smith DF. Multiple domains of the co-chaperone Hop are important for Hsp70 binding. J Biol Chem 2004; 279: 16185-93.
182. Cheung-Flynn J, Roberts PJ, Riggs DL, Smith DF. C-terminal sequences outside the tetratricopeptide repeat domain of FKBP51 and FKBP52 cause differential binding to hsp90. J Biol Chem 2003; 278: 17388-94.
183. Chen SY, Sullivan WP, Toft DO, Smith DF. Differential interactions of p23 and the TPR-containing proteins Hop, Cyp40, FKBP52 and FKBP51 with Hsp90 mutants. Cell Stress & Chaperones 1998; 3: 118-29.
184. Yi F, Zhu PJ, Southall N, et al. An AlphaScreen (TM)-Based High-Throughput Screen to Identify Inhibitors of Hsp90-Cochaperone Interaction. J Biomol Screen 2009; 14: 273-81.
185. Vasko RC, Rodriguez RA, Cunningham CN, Ardi VC, Agard DA, McAlpine SR. Mechanistic Studies of Sansalvamide A-Amide: An Allosteric Modulator of Hsp90. ACS Med Chem Lett 2010; 1: 4-8.
186. Ardi VC, Alexander LD, Johnson VA, McAlpine SR. Macrocycles That Inhibit the Binding between Heat Shock Protein 90 and TPRContaining Proteins. ACS Chem Biol 2011; 6: 1357-66.
187. Schreiber SL. Target-oriented and diversity-oriented organic synthesis in drug discovery. Science 2000; 287: 1964-9.