Chaperoning proteins for destruction: Diverse roles of Hsp70 chaperones and their co-chaperones in targeting misfolded proteins to the proteasome

Biomolecules

Volumn 4, Issue 3, 2014, Pages 704-724

  Shiber, Ayala ^a   Ravid, Tommer ^a  

^a HEBREW UNIVERSITY OF JERUSALEM   (Israel)

Author keywords

Hsp40; Hsp70; Molecular chaperones; Protein aggregation; Protein degradation; Protein misfolding; The Ub proteasome system; Yeast

Indexed keywords

ALPHA SYNUCLEIN; AMYLOID BETA PROTEIN[1-42]; ATAXIN 1; BCL2 ASSOCIATED ATHANOGENE 1 PROTEIN; C TERMINUS OF HEAT SHOCK COGNATE 70 STRESS PROTEIN INTERACTING PROTEIN; COPPER ZINC SUPEROXIDE DISMUTASE; CYSTIC FIBROSIS TRANSMEMBRANE CONDUCTANCE REGULATOR; HEAT SHOCK PROTEIN 40; HEAT SHOCK PROTEIN 70; HSJ1 PROTEIN; HUNTINGTIN; MEMBRANE PROTEIN; NUCLEOTIDE EXCHANGE FACTOR; PROTEASOME; SECRETORY PROTEIN; SIS1 PROTEIN; UBIQUITIN PROTEIN LIGASE E3; UNCLASSIFIED DRUG; UBIQUITIN;

AGING; CELL MEMBRANE; DEGENERATIVE DISEASE; ENDOPLASMIC RETICULUM; ENZYME ACTIVITY; HUMAN; NONHUMAN; PROTEIN AGGREGATION; PROTEIN BINDING; PROTEIN DEGRADATION; PROTEIN EXPRESSION; PROTEIN FOLDING; REVIEW; UBIQUITINATION; ANIMAL; METABOLISM; PROTEOSTASIS DEFICIENCY;

ANIMALS; HSP40 HEAT-SHOCK PROTEINS; HSP70 HEAT-SHOCK PROTEINS; HUMANS; PROTEASOME ENDOPEPTIDASE COMPLEX; PROTEOSTASIS DEFICIENCIES; UBIQUITIN;

EID: 84925503504     PISSN: None     EISSN: 2218273X     Source Type: Journal    
DOI: 10.3390/biom4030704     Document Type: Review

References (111)

1. Hartl, F.U.; Hayer-Hartl, M. Converging concepts of protein folding in vitro and in vivo. Nat. Struct. Mol. Biol. 2009, 16, 574-581.
2. Klionsky, D.J.; Emr, S.D. Autophagy as a regulated pathway of cellular degradation. Science 2000, 290, 1717-1721.
3. Nickell, S.; Beck, F.; Scheres, S.H.; Korinek, A.; Forster, F.; Lasker, K.; Mihalache, O.; Sun, N.; Nagy, I.; Sali, A.; et al. Insights into the molecular architecture of the 26S proteasome. Proc. Natl. Acad. Sci. USA 2009, 106, 11943-11947.
4. Ritossa, F. A new puffing pattern induced by temperature shock and DNP in Drosophila. Experientia 1962, 18, 571-573.
5. Spradling, A.; Penman, S.; Pardue, M.L. Analysis of Drosophila mRNA by in situ hybridization: Sequences transcribed in normal and heat shocked cultured cells. Cell 1975, 4, 395-404.
6. Schedl, P.; Artavanis-Tsakonas, S.; Steward, R.; Gehring, W.J.; Mirault, M.E.; Goldschmidt-Clermont, M.; Moran, L.; Tissieres, A. Two hybrid plasmids with D. Melanogaster DNA sequences complementary to mRNA coding for the major heat shock protein. Cell 1978, 14, 921-929.
7. Ritossa, F. Discovery of the heat shock response. Cell Stress Chaperones 1996, 1, 97-98.
8. Picard, D. Heat-shock protein 90, a chaperone for folding and regulation. Cell. Mol. Life Sci. 2002, 59, 1640-1648.
9. Dworniczak, B.; Mirault, M.E. Structure and expression of a human gene coding for a 71 kd heat shock "cognate" protein. Nucleic Acids Res. 1987, 15, 5181-5197.
10. Hartl, F.U.; Bracher, A.; Hayer-Hartl, M. Molecular chaperones in protein folding and proteostasis. Nature 2011, 475, 324-332.
11. Buchner, J. Supervising the fold: Functional principles of molecular chaperones. FASEB J. 1996, 10, 10-19.
12. Muchowski, P.J.; Wacker, J.L. Modulation of neurodegeneration by molecular chaperones. Nat. Rev. Neurosci. 2005, 6, 11-22.
13. Goldberg, A.L. Protein degradation and protection against misfolded or damaged proteins. Nature 2003, 426, 895-899.
14. Hochstrasser, M. Ubiquitin-dependent protein degradation. Annu. Rev. Genet. 1996, 30, 405-439.
15. Hershko, A.; Ciechanover, A. The ubiquitin system. Annu. Rev. Biochem. 1998, 67, 425-479.
16. Bercovich, B.; Stancovski, I.; Mayer, A.; Blumenfeld, N.; Laszlo, A.; Schwartz, A.L.; Ciechanover, A. Ubiquitin-dependent degradation of certain protein substrates in vitro requires the molecular chaperone Hsc70. J. Biol. Chem. 1997, 272, 9002-9010.
17. Kriegenburg, F.; Ellgaard, L.; Hartmann-Petersen, R. Molecular chaperones in targeting misfolded proteins for ubiquitin-dependent degradation. FEBS J. 2012, 279, 532-542.
18. Shiber, A.; Breuer, W.; Brandeis, M.; Ravid, T. Ubiquitin conjugation triggers misfolded protein sequestration into quality control foci when Hsp70 chaperone levels are limiting. Mol. Biol. Cell 2013, 24, 2076-2087.
19. Park, S.-H.; Bolender, N.; Eisele, F.; Kostova, Z.; Takeuchi, J.; Coffino, P.; Wolf, D.H. The cytoplasmic Hsp70 chaperone machinery subjects misfolded and endoplasmic reticulum import-incompetent proteins to degradation via the ubiquitin-proteasome system. Mol. Biol. Cell 2007, 18, 153-165.
20. Xilouri, M.; Brekk, O.R.; Stefanis, L. Alpha-synuclein and protein degradation systems: A reciprocal relationship. Mol. Neurobiol. 2013, 47, 537-551.
21. Ellis, R.J.; van der Vies, S.M.; Hemmingsen, S.M. The molecular chaperone concept. Biochem. Soc. Symp. 1989, 55, 145-153.
22. Hartl, F.U.; Hayer-Hartl, M. Molecular chaperones in the cytosol: From nascent chain to folded protein. Science 2002, 295, 1852-1858.
23. Morimoto, R.I.; Kline, M.P.; Bimston, D.N.; Cotto, J.J. The heat-shock response: Regulation and function of heat-shock proteins and molecular chaperones. Essays Biochem. 1997, 32, 17-29.
24. Esser, C.; Alberti, S.; Hohfeld, J. Cooperation of molecular chaperones with the ubiquitin/proteasome system. Biochim. Biophys. Acta 2004, 1695, 171-188.
25. Stolz, A.; Wolf, D.H. Endoplasmic reticulum associated protein degradation: A chaperone assisted journey to hell. Biochim. Biophys. Acta 2010, 1803, 694-705.
26. Ravid, T.; Hochstrasser, M. Diversity of degradation signals in the ubiquitin-proteasome system. Nat. Rev. Mol. Cell Biol. 2008, 9, 679-689.
27. Kampinga, H.H.; Craig, E.A. The Hsp70 chaperone machinery: J proteins as drivers of functional specificity. Nat. Rev. Mol. Cell Biol. 2010, 11, 579-592.
28. Qiu, X.B.; Shao, Y.M.; Miao, S.; Wang, L. The diversity of the DnaJ/Hsp40 family, the crucial partners for Hsp70 chaperones. Cell. Mol. Life Sci. 2006, 63, 2560-2570.
29. Kettern, N.; Dreiseidler, M.; Tawo, R.; Hohfeld, J. Chaperone-assisted degradation: Multiple paths to destruction. Biol. Chem. 2010, 391, 481-489.
30. Arndt, V.; Rogon, C.; Hohfeld, J. To be, or not to be-Molecular chaperones in protein degradation. Cell. Mol. Life Sci. 2007, 64, 2525-2541.
31. Simons, J.F.; Ferro-Novick, S.; Rose, M.D.; Helenius, A. BiP/Kar2p serves as a molecular chaperone during carboxypeptidase Y folding in yeast. J. Cell Biol. 1995, 130, 41-49.
32. Plemper, R.K.; Bohmler, S.; Bordallo, J.; Sommer, T.; Wolf, D.H. Mutant analysis links the translocon and bip to retrograde protein transport for ER degradation. Nature 1997, 388, 891-895.
33. Nishikawa, S.; Brodsky, J.L.; Nakatsukasa, K. Roles of molecular chaperones in endoplasmic reticulum (ER) quality control and ER-associated degradation (ERAD). J. Biochem. 2005, 137, 551-555.
34. Venkatraman, P.; Wetzel, R.; Tanaka, M.; Nukina, N.; Goldberg, A.L. Eukaryotic proteasomes cannot digest polyglutamine sequences and release them during degradation of polyglutamine-containing proteins. Mol. Cell 2004, 14, 95-104.
35. Nakatsukasa, K.; Huyer, G.; Michaelis, S.; Brodsky, J.L. Dissecting the ER-associated degradation of a misfolded polytopic membrane protein. Cell 2008, 132, 101-112.
36. McClellan, A.J.; Scott, M.D.; Frydman, J. Folding and quality control of the VHL tumor suppressor proceed through distinct chaperone pathways. Cell 2005, 121, 739-748.
37. Huyer, G.; Piluek, W.F.; Fansler, Z.; Kreft, S.G.; Hochstrasser, M.; Brodsky, J.L.; Michaelis, S. Distinct machinery is required in saccharomyces cerevisiae for the endoplasmic reticulum-associated degradation of a multispanning membrane protein and a soluble luminal protein. J. Biol. Chem. 2004, 279, 38369-38378.
38. Metzger, M.B.; Maurer, M.J.; Dancy, B.M.; Michaelis, S. Degradation of a cytosolic protein requires endoplasmic reticulum-associated degradation machinery. J. Biol. Chem. 2008, 283, 32302-32316.
39. Liberek, K.; Marszalek, J.; Ang, D.; Georgopoulos, C.; Zylicz, M. Escherichia coli DnaJ and GrpE heat shock proteins jointly stimulate ATPase activity of DnaK. Proc. Natl. Acad. Sci. USA 1991, 88, 2874-2878.
40. Buck, T.M.; Kolb, A.R.; Boyd, C.R.; Kleyman, T.R.; Brodsky, J.L. The endoplasmic reticulum-associated degradation of the epithelial sodium channel requires a unique complement of molecular chaperones. Mol. Biol. Cell 2010, 21, 1047-1058.
41. Cyr, D.M. Cooperation of the molecular chaperone Ydj1 with specific Hsp70 homologs to suppress protein aggregation. FEBS Lett. 1995, 359, 129-132.
42. Summers, D.W.; Wolfe, K.J.; Ren, H.Y.; Cyr, D.M. The type II Hsp40 Sis1 cooperates with Hsp70 and the E3 ligase Ubr1 to promote degradation of terminally misfolded cytosolic protein. PLoS One 2013, 8, e52099.
43. Lee, D.H.; Sherman, M.Y.; Goldberg, A.L. Involvement of the molecular chaperone Ydj1 in the ubiquitin-dependent degradation of short-lived and abnormal proteins in saccharomyces cerevisiae. Mol. Cell. Biol. 1996, 16, 4773-4781.
44. Connell, P.; Ballinger, C.A.; Jiang, J.; Wu, Y.; Thompson, L.J.; Hohfeld, J.; Patterson, C. The co-chaperone CHIP regulates protein triage decisions mediated by heat-shock proteins. Nat. Cell Biol. 2001, 3, 93-96.
45. Murata, S.; Minami, Y.; Minami, M.; Chiba, T.; Tanaka, K. CHIP is a chaperone-dependent E3 ligase that ubiquitylates unfolded protein. EMBO Rep. 2001, 2, 1133-1138.
46. Ballinger, C.A.; Connell, P.; Wu, Y.; Hu, Z.; Thompson, L.J.; Yin, L.Y.; Patterson, C. 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, 4535-4545.
47. Jiang, J.; Ballinger, C.A.; Wu, Y.; Dai, Q.; Cyr, D.M.; Hohfeld, J.; Patterson, C. CHIP is a U-box-dependent E3 ubiquitin ligase: Identification of Hsc70 as a target for ubiquitylation. J. Biol. Chem. 2001, 276, 42938-42944.
48. Zhou, P.; Fernandes, N.; Dodge, I.L.; Reddi, A.L.; Rao, N.; Safran, H.; DiPetrillo, T.A.; Wazer, D.E.; Band, V.; Band, H. ErbB2 degradation mediated by the co-chaperone protein CHIP. J. Biol. Chem. 2003, 278, 13829-13837.
49. Shimura, H.; Schwartz, D.; Gygi, S.P.; Kosik, K.S. CHIP-Hsc70 complex ubiquitinates phosphorylated tau and enhances cell survival. J. Biol. Chem. 2004, 279, 4869-4876.
50. Meacham, G.C.; Patterson, C.; Zhang, W.; Younger, J.M.; Cyr, D.M. The Hsc70 co-chaperone chip targets immature CFTR for proteasomal degradation. Nat. Cell Biol. 2001, 3, 100-105.
51. Kerem, B.; Rommens, J.M.; Buchanan, J.A.; Markiewicz, D.; Cox, T.K.; Chakravarti, A.; Buchwald, M.; Tsui, L.C. Identification of the cystic fibrosis gene: Genetic analysis. Science 1989, 245, 1073-1080.
52. Lukacs, G.L.; Mohamed, A.; Kartner, N.; Chang, X.B.; Riordan, J.R.; Grinstein, S. Conformational maturation of CFTR but not its mutant counterpart (delta F508) occurs in the endoplasmic reticulum and requires ATP. EMBO J. 1994, 13, 6076-6086.
53. Du, K.; Sharma, M.; Lukacs, G.L. The deltaF508 cystic fibrosis mutation impairs domain-domain interactions and arrests post-translational folding of CFTR. Nat. Struct. Mol. Biol. 2005, 12, 17-25.
54. Younger, J.M.; Chen, L.; Ren, H.Y.; Rosser, M.F.; Turnbull, E.L.; Fan, C.Y.; Patterson, C.; Cyr, D.M. Sequential quality-control checkpoints triage misfolded cystic fibrosis transmembrane conductance regulator. Cell 2006, 126, 571-582.
55. Szabo, A.; Langer, T.; Schröder, H.; Flanagan, J.; Bukau, B.; Hartl, F.U. The ATP hydrolysis-dependent reaction cycle of the Escherichia coli Hsp70 system DnaK, DnaJ, and GrpE. Proc. Natl. Acad. Sci. USA 1994, 91, 10345-10349.
56. Alberti, S.; Bohse, K.; Arndt, V.; Schmitz, A.; Hohfeld, J. The cochaperone HspBP1 inhibits the CHIP ubiquitin ligase and stimulates the maturation of the cystic fibrosis transmembrane conductance regulator. Mol. Biol. Cell 2004, 15, 4003-4010.
57. Dai, Q.; Qian, S.B.; Li, H.H.; McDonough, H.; Borchers, C.; Huang, D.; Takayama, S.; Younger, J.M.; Ren, H.Y.; Cyr, D.M.; et al. Regulation of the cytoplasmic quality control protein degradation pathway by BAG2. J. Biol. Chem. 2005, 280, 38673-38681.
58. 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, 5891-5900.
59. Morito, D.; Hirao, K.; Oda, Y.; Hosokawa, N.; Tokunaga, F.; Cyr, D.M.; Tanaka, K.; Iwai, K.; Nagata, K. Gp78 cooperates with RMA1 in endoplasmic reticulum-associated degradation of cftrδF508. Mol. Biol. Cell 2008, 19, 1328-1336.
60. Cheng, J.; Guggino, W. Ubiquitination and degradation of CFTR by the E3 ubiquitin ligase MARCH2 through its association with adaptor proteins CAL and STX6. PLoS One 2013, 8, e68001.
61. Youker, R.T.; Walsh, P.; Beilharz, T.; Lithgow, T.; Brodsky, J.L. Distinct roles for the Hsp40 and Hsp90 molecular chaperones during cystic fibrosis transmembrane conductance regulator degradation in yeast. Mol. Biol. Cell 2004, 15, 4787-4797.
62. Grove, D.E.; Fan, C.-Y.; Ren, H.Y.; Cyr, D.M. The endoplasmic reticulum-associated Hsp40 DnaJB12 and Hsc70 cooperate to facilitate RMA1 E3-dependent degradation of nascent cftrδF508. Mol. Biol. Cell 2011, 22, 301-314.
63. Raviol, H.; Sadlish, H.; Rodriguez, F.; Mayer, M.P.; Bukau, B. Chaperone network in the yeast cytosol: Hsp110 is revealed as an Hsp70 nucleotide exchange factor. EMBO J. 2006, 25, 2510-2518.
64. Gowda, N.K.C.; Kandasamy, G.; Froehlich, M.S.; Dohmen, R.J.; Andréasson, C. Hsp70 nucleotide exchange factor Fes1 is essential for ubiquitin-dependent degradation of misfolded cytosolic proteins. Proc. Natl. Acad. Sci. USA 2013, 110, 5975-5980.
65. Eisele, F.; Wolf, D.H. Degradation of misfolded protein in the cytoplasm is mediated by the ubiquitin ligase UBR1. FEBS Lett. 2008, 582, 4143-4146.
66. Gardner, R.G.; Nelson, Z.W.; Gottschling, D.E. Degradation-mediated protein quality control in the nucleus. Cell 2005, 120, 803-815.
67. Heck, J.W.; Cheung, S.K.; Hampton, R.Y. Cytoplasmic protein quality control degradation mediated by parallel actions of the E3 ubiquitin ligases Ubr1 and San1. Proc. Natl. Acad. Sci. USA 2010, 107, 1106-1111.
68. Rosenbaum, J.C.; Fredrickson, E.K.; Oeser, M.L.; Garrett-Engele, C.M.; Locke, M.N.; Richardson, L.A.; Nelson, Z.W.; Hetrick, E.D.; Milac, T.I.; Gottschling, D.E.; et al. Disorder targets misorder in nuclear quality control degradation: A disordered ubiquitin ligase directly recognizes its misfolded substrates. Mol. Cell 2011, 41, 93-106.
69. Prasad, R.; Kawaguchi, S.; Ng, D.T. A nucleus-based quality control mechanism for cytosolic proteins. Mol. Biol. Cell 2010, 21, 2117-2127.
70. Guerriero, C.J.; Weiberth, K.F.; Brodsky, J.L. Hsp70 targets a cytoplasmic quality control substrate to the san1p ubiquitin ligase. J. Biol. Chem. 2013, 288, 18506-18520.
71. Shorter, J.; Lindquist, S. Hsp104, Hsp70 and Hsp40 interplay regulates formation, growth and elimination of Sup35 prions. EMBO J. 2008, 27, 2712-2724.
72. Summers, D.W.; Douglas, P.M.; Cyr, D.M. Prion propagation by Hsp40 molecular chaperones. Prion 2009, 3, 59-64.
73. Park, S.H.; Kukushkin, Y.; Gupta, R.; Chen, T.; Konagai, A.; Hipp, M.S.; Hayer-Hartl, M.; Hartl, F.U. Polyq proteins interfere with nuclear degradation of cytosolic proteins by sequestering the Sis1P chaperone. Cell 2013, 154, 134-145.
74. Furth, N.; Gertman, O.; Shiber, A.; Alfassy, O.S.; Cohen, I.; Rosenberg, M.M.; Doron, N.K.; Friedler, A.; Ravid, T. Exposure of bipartite hydrophobic signal triggers nuclear quality control of Ndc10 at the endoplasmic reticulum/nuclear envelope. Mol. Biol. Cell 2011, 22, 4726-4739.
75. Oling, D.; Eisele, F.; Kvint, K.; Nystrom, T. Opposing roles of Ubp3-dependent deubiquitination regulate replicative life span and heat resistance. EMBO J. 2014, 33, 747-761.
76. Cummings, C.J.; Mancini, M.A.; Antalffy, B.; DeFranco, D.B.; Orr, H.T.; Zoghbi, H.Y. Chaperone suppression of aggregation and altered subcellular proteasome localization imply protein misfolding in Sca1. Nat. Genet. 1998, 19, 148-154.
77. Bailey, C.K.; Andriola, I.F.; Kampinga, H.H.; Merry, D.E. Molecular chaperones enhance the degradation of expanded polyglutamine repeat androgen receptor in a cellular model of spinal and bulbar muscular atrophy. Hum. Mol. Genet. 2002, 11, 515-523.
78. Wang, Q.; Liu, Y.; Soetandyo, N.; Baek, K.; Hegde, R.; Ye, Y. A ubiquitin ligase-associated chaperone holdase maintains polypeptides in soluble states for proteasome degradation. Mol. Cell 2011, 42, 758-770.
79. Takayama, S.; Sato, T.; Krajewski, S.; Kochel, K.; Irie, S.; Milian, J.A.; Reed, J.C. Cloning and functional analysis of BAG-1: A novel Bcl-2-binding protein with anti-cell death activity. Cell 1995, 80, 279-284.
80. Lüders, J.; Demand, J.; Höhfeld, J. The ubiquitin-related BAG-1 provides a link between the molecular chaperones Hsc70/Hsp70 and the proteasome. J. Biol. Chem. 2000, 275, 4613-4617.
81. Demand, J.; Alberti, S.; Patterson, C.; Höhfeld, J. Cooperation of a ubiquitin domain protein and an E3 ubiquitin ligase during chaperone/proteasome coupling. Curr. Biol. 2001, 11, 1569-1577.
82. Alberti, S.; Demand, J.; Esser, C.; Emmerich, N.; Schild, H.; Höhfeld, J. Ubiquitylation of BAG-1 suggests a novel regulatory mechanism during the sorting of chaperone substrates to the proteasome. J. Biol. Chem. 2002, 277, 45920-45927.
83. Höhfeld, J.; Jentsch, S. GRPE-like regulation of the Hsc70 chaperone by the anti-apoptotic protein BAG??1. EMBO J. 1997, 16, 6209-6216.
84. Kriegenburg, F.; Jakopec, V.; Poulsen, E.G.; Nielsen, S.V.; Roguev, A.; Krogan, N.; Gordon, C.; Fleig, U.; Hartmann-Petersen, R. A chaperone-assisted degradation pathway targets kinetochore proteins to ensure genome stability. PLoS Genet. 2014, 10, e1004140.
85. Westhoff, B.; Chapple, J.P.; van der Spuy, J.; Höhfeld, J.; Cheetham, M.E. Hsj1 is a neuronal shuttling factor for the sorting of chaperone clients to the proteasome. Curr. Biol. 2005, 15, 1058-1064.
86. Novoselov, S.S.; Mustill, W.J.; Gray, A.L.; Dick, J.R.; Kanuga, N.; Kalmar, B.; Greensmith, L.; Cheetham, M.E. Molecular chaperone mediated late-stage neuroprotection in the SOD1G93A mouse model of amyotrophic lateral sclerosis. PLoS One 2013, 8, e73944.
87. Gao, X.-C.; Zhou, C.-J.; Zhou, Z.-R.; Zhang, Y.-H.; Zheng, X.-M.; Song, A.-X.; Hu, H.-Y. Co-chaperone HSJ1a dually regulates the proteasomal degradation of ataxin-3. PLoS One 2011, 6, e19763.
88. Urushitani, M.; Kurisu, J.; Tateno, M.; Hatakeyama, S.; Nakayama, K.-I.; Kato, S.; Takahashi, R. CHIP promotes proteasomal degradation of familial ALS-linked mutant SOD1 by ubiquitinating Hsp/Hsc70. J. Neurochem. 2004, 90, 231-244.
89. Kundrat, L.; Regan, L. Identification of residues on Hsp70 and Hsp90 ubiquitinated by the cochaperone CHIP. J. Mol. Biol. 2010, 395, 587-594.
90. Peng, J.; Schwartz, D.; Elias, J.E.; Thoreen, C.C.; Cheng, D.; Marsischky, G.; Roelofs, J.; Finley, D.; Gygi, S.P. A proteomics approach to understanding protein ubiquitination. Nat. Biotechnol. 2003, 21, 921-926.
91. Muchowski, P.J.; Schaffar, G.; Sittler, A.; Wanker, E.E.; Hayer-Hartl, M.K.; Hartl, F.U. Hsp70 and Hsp40 chaperones can inhibit self-assembly of polyglutamine proteins into amyloid-like fibrils. Proc. Natl. Acad. Sci. USA 2000, 97, 7841-7846.
92. Klucken, J.; Shin, Y.; Masliah, E.; Hyman, B.T.; McLean, P.J. Hsp70 reduces alpha-synuclein aggregation and toxicity. J. Biol. Chem. 2004, 279, 25497-25502.
93. Evans, C.G.; Wisen, S.; Gestwicki, J.E. Heat shock proteins 70 and 90 inhibit early stages of amyloid beta-(1-42) aggregation in vitro. J. Biol. Chem. 2006, 281, 33182-33191.
94. Sørensen, J.G.; Loeschcke, V. Decreased heat-shock resistance and down-regulation of Hsp70 expression with increasing age in adult Drosophila melanogaster. Funct. Ecol. 2002, 16, 379-384.
95. Ben-Zvi, A.; Miller, E.A.; Morimoto, R.I. Collapse of proteostasis represents an early molecular event in caenorhabditis elegans aging. Proc. Natl. Acad. Sci. USA 2009, 106, 14914-14919.
96. Hebert, L.E.; Scherr, P.A.; Beckett, L.A.; Albert, M.S.; Pilgrim, D.M.; Chown, M.J.; Funkenstein, H.H.; Evans, D.A. Age-specific incidence of Alzheimer’s disease in a community population. JAMA 1995, 273, 1354-1359.
97. Cao, K.; Chen-Plotkin, A.S.; Plotkin, J.B.; Wang, L.-S. Age-correlated gene expression in normal and neurodegenerative human brain tissues. PLoS One 2010, 5, e13098.
98. Ciechanover, A. The ubiquitin proteolytic system and pathogenesis of human diseases: A novel platform for mechanism-based drug targeting. Biochem. Soc. Trans. 2003, 31, 474-481.
99. Cipriani, G.; Dolciotti, C.; Picchi, L.; Bonuccelli, U. Alzheimer and his disease: A brief history. Neurol. Sci. 2011, 32, 275-279.
100. Woulfe, J.M. Abnormalities of the nucleus and nuclear inclusions in neurodegenerative disease: A work in progress. Neuropathol. Appl. Neurobiol. 2007, 33, 2-42.
101. Chhangani, D.; Jana, N.R.; Mishra, A. Misfolded proteins recognition strategies of E3 ubiquitin ligases and neurodegenerative diseases. Mol. Neurobiol. 2012, 47, 302-312.
102. Calise, J.; Powell, S.R. The ubiquitin proteasome system and myocardial Ischemia. Am. J. Physiol. Heart Circ. Physiol. 2013, 304, H337-H349.
103. Vilchez, D.; Morantte, I.; Liu, Z.; Douglas, P.M.; Merkwirth, C.; Rodrigues, A.P.; Manning, G.; Dillin, A. RPN-6 determines C. Elegans longevity under proteotoxic stress conditions. Nature 2012, 489, 263-268.
104. Vilchez, D.; Boyer, L.; Morantte, I.; Lutz, M.; Merkwirth, C.; Joyce, D.; Spencer, B.; Page, L.; Masliah, E.; Berggren, W.T.; et al. Increased proteasome activity in human embryonic stem cells is regulated by PSMD11. Nature 2012, 489, 304-308.
105. Xie, Y.; Wolff, D.W.; Wei, T.; Wang, B.; Deng, C.; Kirui, J.K.; Jiang, H.; Qin, J.; Abel, P.W.; Tu, Y. Breast cancer migration and invasion depend on proteasome degradation of regulator of G-protein signaling 4. Cancer Res. 2009, 69, 5743-5751.
106. Marber, M.S.; Mestril, R.; Chi, S.H.; Sayen, M.R.; Yellon, D.M.; Dillmann, W.H. Overexpression of the rat inducible 70-kd heat stress protein in a transgenic mouse increases the resistance of the heart to ischemic injury. J. Clin. Investig. 1995, 95, 1446-1456.
107. Cummings, C.J.; Sun, Y.; Opal, P.; Antalffy, B.; Mestril, R.; Orr, H.T.; Dillmann, W.H.; Zoghbi, H.Y. Over-expression of inducible Hsp70 chaperone suppresses neuropathology and improves motor function in Sca1 mice. Hum. Mol. Genet. 2001, 10, 1511-1518.
108. Nylandsted, J.; Rohde, M.; Brand, K.; Bastholm, L.; Elling, F.; 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, 7871-7876.
109. Saluja, A.; Dudeja, V. Heat shock proteins in pancreatic diseases. J. Gastroenterol. Hepatol. 2008, 23, S42-S45.
110. Labbadia, J.; Novoselov, S.S.; Bett, J.S.; Weiss, A.; Paganetti, P.; Bates, G.P.; Cheetham, M.E. Suppression of protein aggregation by chaperone modification of high molecular weight complexes. Brain 2012, 135, 1180-1196.
111. Grove, D.E.; Rosser, M.F.; Ren, H.Y.; Naren, A.P.; Cyr, D.M. Mechanisms for rescue of correctable folding defects in cftrdelta F508. Mol. Biol. Cell 2009, 20, 4059-4069.