Protein homeostasis as a therapeutic target for diseases of protein conformation

Current Topics in Medicinal Chemistry

Volumn 12, Issue 22, 2012, Pages 2623-2640

  Calamini, Barbara ^a   Morimoto, Richard I ^b  

^a DUKE UNIVERSITY SCHOOL OF MEDICINE   (United States)

^b NORTHWESTERN UNIVERSITY   (United States)

Author keywords

Protein conformational diseases; Proteostasis network; Proteostasis regulators; Stress responses

Indexed keywords

ACTIVATING TRANSCRIPTION FACTOR 6; BORTEZOMIB; CALRETICULIN; CARBAMAZEPINE; CHAPERONE; CURCUMIN; DANTROLENE; DILTIAZEM; GELDANAMYCIN; GLUCOSIDASE; GUANABENZ; HEAT SHOCK PROTEIN 70; HEAT SHOCK PROTEIN 90 INHIBITOR; HEAT SHOCK TRANSCRIPTION FACTOR 1; HISTONE DEACETYLASE; LACIDIPINE; LITHIUM; NONSTEROID ANTIINFLAMMATORY AGENT; PHENOXAZINE DERIVATIVE; PROTEASOME INHIBITOR; PROTEIN IRE1; RAPAMYCIN; RYANODINE; SALICYLATE SODIUM; THAPSIGARGIN; TREHALOSE; UBIQUITIN; UNINDEXED DRUG; VALPROIC ACID; VERAPAMIL;

ARTICLE; AUTOPHAGY; CALCIUM SIGNALING; DISEASE COURSE; DNA BINDING; ENDOPLASMIC RETICULUM ASSOCIATED DEGRADATION; HEAT SHOCK RESPONSE; HUMAN; LYSOSOME STORAGE DISEASE; METABOLIC STRESS; NONHUMAN; PHASE 1 CLINICAL TRIAL (TOPIC); PHASE 3 CLINICAL TRIAL (TOPIC); PROTEIN CONFORMATION; PROTEIN DEGRADATION; PROTEIN FOLDING; PROTEIN HOMEOSTASIS; PROTEIN MISFOLDING; UNFOLDED PROTEIN RESPONSE;

AUTOPHAGY; HEAT-SHOCK RESPONSE; HISTONE DEACETYLASE INHIBITORS; HOMEOSTASIS; HUMANS; MOLECULAR CHAPERONES; MOLECULAR TARGETED THERAPY; PROTEASOME INHIBITORS; PROTEIN CONFORMATION; PROTEIN FOLDING; PROTEINS; PROTEOSTASIS DEFICIENCIES;

EID: 84874832163     PISSN: 15680266     EISSN: 18734294     Source Type: Journal    
DOI: 10.2174/1568026611212220014     Document Type: Article

References (164)

1. Balch W. E.; Morimoto R. I.; Dillin A.; Kelly J. W. Adapting pro-teostasis for disease intervention. Science, 2008, 319 (5865) 916-919.
2. Walter P.; Ron D. The unfolded protein response: from stress pathway to homeostatic regulation. Science, 2011, 334 (6059) 1081-1086.
3. Baker M. J.; Tatsuta T.; Langer T. Quality control of mitochondrial proteostasis. Cold Spring Harbor Perspect. Biol., 2011, 3 (7).
4. Powers E. T.; Morimoto R. I.; Dillin A.; Kelly J. W.; Balch W. E. Biological and chemical approaches to diseases of proteostasis deficiency. Annual review of biochemistry, 2009, 78 959-991.
5. Gidalevitz T.; Ben-Zvi A.; Ho K. H.; Brignull H. R.; Morimoto R. I. Progressive disruption of cellular protein folding in models of polyglutamine diseases. Science, 2006, 311 (5766) 1471-1474.
6. Gidalevitz T.; Krupinski T.; Garcia S.; Morimoto R. I. Destabilizing protein polymorphisms in the genetic background direct pheno-typic expression of mutant SOD1 toxicity. PLoS Genet., 2009, 5 (3) e1000399.
7. Gidalevitz T.; Kikis E. A.; Morimoto R. I. A cellular perspective on conformational disease: the role of genetic background and proteo-stasis networks. Curr. Opin. Struct. Biol., 2010, 20 (1) 23-32.
8. Cohen F. E.; Kelly J. W. Therapeutic approaches to protein-misfolding diseases. Nature, 2003, 426 (6968) 905-909.
9. Fan J. Q.; Ishii S.; Asano N.; Suzuki Y. Accelerated transport and maturation of lysosomal alpha-galactosidase A in Fabry lym-phoblasts by an enzyme inhibitor. Nat. Med., 1999, 5 (1) 112-115.
10. Qu B. H.; Strickland E. H.; Thomas P. J. Localization and suppression of a kinetic defect in cystic fibrosis transmembrane conductance regulator folding. J. Biol. Chem., 1997, 272 (25) 15739-15744.
11. Cohen E.; Bieschke J.; Perciavalle R. M.; Kelly J. W.; Dillin A. Opposing activities protect against age-onset proteotoxicity. Science, 2006, 313 (5793) 1604-1610.
12. Desnick R. J.; Schuchman E. H. Enzyme replacement and enhancement therapies: lessons from lysosomal disorders. Nat. Rev. Genet., 2002, 3 (12) 954-966.
13. Kalinderi K.; Fidani L.; Katsarou Z.; Bostantjopoulou S. Pharmacological treatment and the prospect of pharmacogenetics in Parkinson's disease. Int. J. Clin. Pract., 2011, 65 (12) 1289-1294.
14. Boillee S.; Vande Velde C.; Cleveland D. W. ALS: a disease of motor neurons and their nonneuronal neighbors. Neuron, 2006, 52 (1) 39-59.
15. Walker F. O. Huntington's disease. Lancet, 2007, 369 (9557) 218-228.
16. Lindquist S. L.; Kelly J. W. Chemical and biological approaches for adapting proteostasis to ameliorate protein misfolding and aggregation diseases: progress and prognosis. Cold Spring Harb. Perspect. Biol., 2011, 3 (12).
17. Luo W.; Sun W.; Taldone T.; Rodina A.; Chiosis G. Heat shock protein 90 in neurodegenerative diseases. Mol. Neurodegener., 2010, 5 24.
18. Brodsky J. L.; Chiosis G. Hsp70 molecular chaperones: emerging roles in human disease and identification of small molecule modulators. Curr. Top. Med. Chem., 2006, 6 (11) 1215-1225.
19. Morley J. F.; Brignull H. R.; Weyers J. J.; Morimoto R. I. The threshold for polyglutamine-expansion protein aggregation and cellular toxicity is dynamic and influenced by aging in Caenorhabditis elegans. Proc. Natl. Acad. Sci. U. S. A., 2002, 99 (16) 10417-10422.
20. Cohen E.; Paulsson J. F.; Blinder P.; Burstyn-Cohen T.; Du D.; Estepa G.; Adame A.; Pham H. M.; Holzenberger M.; Kelly J. W.; Masliah E.; Dillin A. Reduced IGF-1 signaling delays age-associated proteotoxicity in mice. Cell, 2009, 139 (6) 1157-1169.
21. 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. U. S. A., 2009, 106 (35) 14914-14919.
22. Morimoto R. I.; Cuervo A. M. Protein homeostasis and aging: taking care of proteins from the cradle to the grave. J. Gerontol. A Biol. Sci. Med. Sci., 2009, 64 (2) 167-170.
23. Cohen E.; Du D.; Joyce D.; Kapernick E. A.; Volovik Y.; Kelly J. W.; Dillin A. Temporal requirements of insulin/IGF-1 signaling for proteotoxicity protection. Aging Cell, 2010, 9 (2) 126-134.
24. Akerfelt M.; Morimoto R. I.; Sistonen L. Heat shock factors: integrators of cell stress development and lifespan. Nat. Rev. Mol. Cell Biol., 2010, 11 (8) 545-555.
25. Westerheide S. D.; Morimoto R. I. Heat shock response modulators as therapeutic tools for diseases of protein conformation. J. Biol. Chem., 2005, 280 (39) 33097-33100.
26. Hietakangas V.; Ahlskog J. K.; Jakobsson A. M.; Hellesuo M.; Sahlberg N. M.; Holmberg C. I.; Mikhailov A.; Palvimo J. J.; Pirk-kala L.; Sistonen L. Phosphorylation of serine 303 is a prerequisite for the stress-inducible SUMO modification of heat shock factor 1. Mol. Cell. Biol., 2003, 23 (8) 2953-2968.
27. Hong Y.; Rogers R.; Matunis M. J.; Mayhew C. N.; Goodson M. L.; Park-Sarge O. K.; Sarge K. D. Regulation of heat shock transcription factor 1 by stress-induced SUMO-1 modification. J. Biol. Chem., 2001, 276 (43) 40263-40267.
28. Sandqvist A.; Bjork J. K.; Akerfelt M.; Chitikova Z.; Grichine A.; Vourc'h C.; Jolly C.; Salminen T. A.; Nymalm Y.; Sistonen L. Het-erotrimerization of heat-shock factors 1 and 2 provides a transcrip-tional switch in response to distinct stimuli. Mol. Biol. Cell, 2009, 20 (5) 1340-1347.
29. Jurivich D. A.; Sistonen L.; Kroes R. A.; Morimoto R. I. Effect of sodium salicylate on the human heat shock response. Science, 1992, 255 (5049) 1243-1245.
30. Lee B. S.; Chen J.; Angelidis C.; Jurivich D. A.; Morimoto R. I. Pharmacological modulation of heat shock factor 1 by antiinflam-matory drugs results in protection against stress-induced cellular damage. Proc. Natl. Acad. Sci. U. S. A., 1995, 92 (16) 7207-7211.
31. Jurivich D. A.; Sistonen L.; Sarge K. D.; Morimoto R. I. Arachido-nate is a potent modulator of human heat shock gene transcription. Proc. Natl. Acad. Sci. U. S. A., 1994, 91 (6) 2280-2284.
32. Amici C.; Sistonen L.; Santoro M. G.; Morimoto R. I. Antiprolif-erative prostaglandins activate heat shock transcription factor. Proc. Natl. Acad. Sci. U. S. A., 1992, 89 (14) 6227-6231.
33. Neef D. W.; Jaeger A. M.; Thiele D. J. Heat shock transcription factor 1 as a therapeutic target in neurodegenerative diseases. Nat. Rev. Drug Discov., 2011, 10 (12) 930-944.
34. Dick L. R.; Fleming P. E. Building on bortezomib: second-generation proteasome inhibitors as anti-cancer therapy. Drug Dis-cov. Today, 2010, 15 (5/6) 243-249.
35. Holmberg C. I.; Illman S. A.; Kallio M.; Mikhailov A.; Sistonen L. Formation of nuclear HSF1 granules varies depending on stress stimuli. Cell Stress Chaperones, 2000, 5 (3) 219-228.
36. Rossi A.; Elia G.; Santoro M. G. Activation of the heat shock factor 1 by serine protease inhibitors. An effect associated with nuclear factor-kappaB inhibition. J. Biol. Chem., 1998, 273 (26) 16446-16452.
37. Corson T. W.; Crews C. M. Molecular understanding and modern application of traditional medicines: triumphs and trials. Cell, 2007, 130 (5) 769-774.
38. Sethi G.; Ahn K. S.; Pandey M. K.; Aggarwal B. B. Celastrol a novel triterpene potentiates TNF-induced apoptosis and suppresses invasion of tumor cells by inhibiting NF-kappaB-regulated gene products and TAK1-mediated NF-kappaB activation. Blood, 2007, 109 (7) 2727-2735.
39. Cleren C.; Calingasan N. Y.; Chen J.; Beal M. F. Celastrol protects against MPTP- and 3-nitropropionic acid-induced neurotoxicity. J. Neurochem., 2005, 94 (4) 995-1004.
40. Westerheide S. D.; Bosman J. D.; Mbadugha B. N.; Kawahara T. L.; Matsumoto G.; Kim S.; Gu W.; Devlin J. P.; Silverman R. B.; Morimoto R. I. Celastrols as inducers of the heat shock response and cytoprotection. J. Biol. Chem., 2004, 279 (53) 56053-560560.
41. Trott A.; West J. D.; Klaic L.; Westerheide S. D.; Silverman R. B.; Morimoto R. I.; Morano K. A. Activation of heat shock and anti-oxidant responses by the natural product celastrol: transcriptional signatures of a thiol-targeted molecule. Mol. Biol. Cell, 2008, 19 (3) 1104-1112.
42. Zhang T.; Li Y.; Yu Y.; Zou P.; Jiang Y.; Sun D. Characterization of celastrol to inhibit hsp90 and cdc37 interaction. J. Biol. Chem., 2009, 284 (51) 35381-35389.
43. Zhang T.; Hamza A.; Cao X.; Wang B.; Yu S.; Zhan C. G.; Sun D. A novel Hsp90 inhibitor to disrupt Hsp90/Cdc37 complex against pancreatic cancer cells. Mol. Cancer Ther., 2008, 7 (1) 162-170.
44. Hieronymus H.; Lamb J.; Ross K. N.; Peng X. P.; Clement C.; Rodina A.; Nieto M.; Du J.; Stegmaier K.; Raj S. M.; Maloney K. N.; Clardy J.; Hahn W. C.; Chiosis G.; Golub T. R. Gene expression signature-based chemical genomic prediction identifies a novel class of HSP90 pathway modulators. Cancer Cell, 2006, 10 (4) 321-330.
45. Sreeramulu S.; Gande S. L.; Gobel M.; Schwalbe H. Molecular mechanism of inhibition of the human protein complex Hsp90-Cdc37 a kinome chaperone-cochaperone by triterpene celastrol. Angew. Chem. Int. Ed. Engl., 2009, 48 (32) 5853-5855.
46. Chadli A.; Felts S. J.; Wang Q.; Sullivan W. P.; Botuyan M. V.; Fauq A.; Ramirez-Alvarado M.; Mer G. Celastrol inhibits Hsp90 chaperoning of steroid receptors by inducing fibrillization of the Co-chaperone p23. J. Biol. Chem., 2010, 285 (6) 4224-4231.
47. Klaic L.; Morimoto R. I.; Silverman R. B. Celastrol analogues as inducers of the heat shock response. Design and synthesis of affinity probes for the identification of protein targets. ACS Chem. Biol., 2012, 7 (5) 928-937.
48. Yang H.; Chen D.; Cui Q. C.; Yuan X.; Dou Q. P. Celastrol a triterpene extracted from the Chinese Thunder of God Vine is a potent proteasome inhibitor and suppresses human prostate cancer growth in nude mice. Cancer Res., 2006, 66 (9) 4758-4765.
49. Mu T. W.; Ong D. S.; Wang Y. J.; Balch W. E.; Yates J. R. 3rd; Segatori L.; Kelly J. W. Chemical and biological approaches syn-ergize to ameliorate protein-folding diseases. Cell, 2008, 134 (5) 769-781.
50. Trepel J.; Mollapour M.; Giaccone G.; Neckers L. Targeting the dynamic HSP90 complex in cancer. Nat. Rev. Cancer, 2010, 10 (8) 537-549.
51. Zou J.; Guo Y.; Guettouche T.; Smith D. F.; Voellmy R. Repression of heat shock transcription factor HSF1 activation by HSP90 (HSP90 complex) that forms a stress-sensitive complex with HSF1. Cell, 1998, 94 (4) 471-480.
52. Whitesell L.; Lindquist S. L. HSP90 and the chaperoning of cancer. Nat. Rev. Cancer, 2005, 5 (10) 761-772.
53. Sittler A.; Lurz R.; Lueder G.; Priller J.; Lehrach H.; Hayer-Hartl M. K.; Hartl F. U.; Wanker E. E. Geldanamycin activates a heat shock response and inhibits huntingtin aggregation in a cell culture model of Huntington's disease. Hum. Mol. Genet., 2001, 10 (12) 1307-1315.
54. McLean P. J.; Klucken J.; Shin Y.; Hyman B. T. Geldanamycin induces Hsp70 and prevents alpha-synuclein aggregation and toxicity in vitro. Biochem. Biophys. Res. Commun., 2004, 321 (3) 665-669.
55. Batulan Z.; Taylor D. M.; Aarons R. J.; Minotti S.; Doroudchi M. M.; Nalbantoglu J.; Durham H. D. Induction of multiple heat shock proteins and neuroprotection in a primary culture model of familial amyotrophic lateral sclerosis. Neurobiol. Dis., 2006, 24 (2) 213-225.
56. Dou F.; Netzer W. J.; Tanemura K.; Li F.; Hartl F. U.; Takashima A.; Gouras G. K.; Greengard P.; Xu H. Chaperones increase association of tau protein with microtubules. Proc. Natl. Acad. Sci. U. S. A., 2003, 100 (2) 721-726.
57. Auluck P. K.; Bonini N. M. Pharmacological prevention of Parkinson disease in Drosophila. Nat. Med., 2002, 8 (11) 1185-1186.
58. Auluck P. K.; Meulener M. C.; Bonini N. M. Mechanisms of Suppression of {alpha}-Synuclein Neurotoxicity by Geldanamycin in Drosophila. J. Biol. Chem., 2005, 280 (4) 2873-2878.
59. Hay D. G.; Sathasivam K.; Tobaben S.; Stahl B.; Marber M.; Me-stril R.; Mahal A.; Smith D. L.; Woodman B.; Bates G. P. 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 (13) 1389-1405.
60. Fujikake N.; Nagai Y.; Popiel H. A.; Okamoto Y.; Yamaguchi M.; Toda T. Heat shock transcription factor 1-activating compounds suppress polyglutamine-induced neurodegeneration through induction of multiple molecular chaperones. J. Biol. Chem., 2008, 283 (38) 26188-26197.
61. Waza M.; Adachi H.; Katsuno M.; Minamiyama M.; Sang C.; Tanaka F.; Inukai A.; Doyu M.; Sobue G. 17-AAG an Hsp90 inhibitor ameliorates polyglutamine-mediated motor neuron degeneration. Nat. Med., 2005, 11 (10) 1088-1095.
62. Baldo B.; Weiss A.; Parker C. N.; Bibel M.; Paganetti P.; Kaup-mann K. A screen for enhancers of clearance identifies huntingtin as a heat shock protein 90 (Hsp90) client protein. J. Biol. Chem., 2012, 287 (2) 1406-1414.
63. Wang L.; Xie C.; Greggio E.; Parisiadou L.; Shim H.; Sun L.; Chandran J.; Lin X.; Lai C.; Yang W. J.; Moore D. J.; Dawson T. M.; Dawson V. L.; Chiosis G.; Cookson M. R.; Cai H. The chaper-one activity of heat shock protein 90 is critical for maintaining the stability of leucine-rich repeat kinase 2. J. Neurosci., 2008, 28 (13) 3384-3391.
64. Moriwaki Y.; Kim Y. J.; Ido Y.; Misawa H.; Kawashima K.; Endo S.; Takahashi R. L347P PINK1 mutant that fails to bind to Hsp90/Cdc37 chaperones is rapidly degraded in a proteasome-dependent manner. Neurosci. Res., 2008, 61 (1) 43-48.
65. Falsone S. F.; Kungl A. J.; Rek A.; Cappai R.; Zangger K. The molecular chaperone Hsp90 modulates intermediate steps of amyloid assembly of the Parkinson-related protein alpha-synuclein. J. Biol. Chem., 2009, 284 (45) 31190-31199.
66. Luo W.; Dou F.; Rodina A.; Chip S.; Kim J.; Zhao Q.; Moulick K.; Aguirre J.; Wu N.; Greengard P.; Chiosis G. Roles of heat-shock protein 90 in maintaining and facilitating the neurodegenerative phenotype in tauopathies. Proc. Natl. Acad. Sci. U. S. A., 2007, 104 (22) 9511-9516.
67. Dickey C. A.; Kamal A.; Lundgren K.; Klosak N.; Bailey R. M.; Dunmore J.; Ash P.; Shoraka S.; Zlatkovic J.; Eckman C. B.; Patterson C.; Dickson D. W.; Nahman N. S. Jr.; Hutton M.; Burrows F.; Petrucelli L. The high-affinity HSP90-CHIP complex recognizes and selectively degrades phosphorylated tau client proteins. J. Clin. Invest., 2007, 117 (3) 648-658.
68. Labbadia J.; Cunliffe H.; Weiss A.; Katsyuba E.; Sathasivam K.; Seredenina T.; Woodman B.; Moussaoui S.; Frentzel S.; Luthi-Carter R.; Paganetti P.; Bates G. P. Altered chromatin architecture underlies progressive impairment of the heat shock response in mouse models of Huntington disease. J. Clin. Invest., 2011, 121 (8) 3306-3319.
69. Vaughan C. K.; Neckers L.; Piper P. W. Understanding of the Hsp90 molecular chaperone reaches new heights. Nat. Struct. Mol. Biol., 2010, 17 (12) 1400-1404.
70. Ansar S.; Burlison J. A.; Hadden M. K.; Yu X. M.; Desino K. E.; Bean J.; Neckers L.; Audus K. L.; Michaelis M. L.; Blagg B. S. A non-toxic Hsp90 inhibitor protects neurons from Abeta-induced toxicity. Bioorg. Med. Chem. Lett., 2007, 17 (7), 1984-1990.
71. Yu X. M.; Shen G.; Neckers L.; Blake H.; Holzbeierlein J.; Cronk B.; Blagg B. S. Hsp90 inhibitors identified from a library of novo-biocin analogues. J. Am. Chem. Soc., 2005, 127 (37) 12778-12779.
72. Salehi A. H.; Morris S. J.; Ho W. C.; Dickson K. M.; Doucet G.; Milutinovic S.; Durkin J.; Gillard J. W.; Barker P. A. AEG3482 is an antiapoptotic compound that inhibits Jun kinase activity and cell death through induced expression of heat shock protein 70. Chem. Biol., 2006, 13 (2) 213-223.
73. Kimura H.; Yukitake H.; Tajima Y.; Suzuki H.; Chikatsu T.; Mo-rimoto S.; Funabashi Y.; Omae H.; Ito T.; Yoneda Y.; Takizawa M. ITZ-1 a client-selective Hsp90 inhibitor efficiently induces heat shock factor 1 activation. Chem. Biol., 2010, 17 (1) 18-27.
74. Neef D. W.; Turski M. L.; Thiele D. J. Modulation of heat shock transcription factor 1 as a therapeutic target for small molecule intervention in neurodegenerative disease. PLoS Biol., 2010, 8 (1) e1000291.
75. Tam S.; Geller R.; Spiess C.; Frydman J. The chaperonin TRiC controls polyglutamine aggregation and toxicity through subunit-specific interactions. Nat. Cell Biol., 2006, 8 (10) 1155-1162.
76. Tam S.; Spiess C.; Auyeung W.; Joachimiak L.; Chen B.; Poirier M. A.; Frydman J. The chaperonin TRiC blocks a huntingtin sequence element that promotes the conformational switch to aggregation. Nat. Struct. Mol. Biol., 2009, 16 (12) 1279-1285.
77. Neef D. W.; Jaeger A. M.; Thiele D. J. Heat shock transcription factor 1 as a therapeutic target in neurodegenerative diseases. Nat. Rev. Drug Discov., 2011. 10 (12) 930-944.
78. Calamini B.; Silva M. C.; Madoux F.; Hutt D. M.; Khanna S.; Chalfant M. A.; Saldanha S. A.; Hodder P.; Tait B. D.; Garza D.; Balch W. E.; Morimoto R. I. Small-molecule proteostasis regulators for protein conformational diseases. Nat. Chem. Biol., 2011, 8 (2) 185-196.
79. Walter P.; Ron D. The unfolded protein response: from stress pathway to homeostatic regulation. Science, 2011, 334 (6059) 1081-1086.
80. Ron D.; Walter P. Signal integration in the endoplasmic reticulum unfolded protein response. Nat. Rev. Mol. Cell Biol., 2007, 8 (7) 519-529.
81. Volchuk A.; Ron D. The endoplasmic reticulum stress response in the pancreatic beta-cell. Diabetes. Obes. Metab., 2010, 12 Suppl 248-257.
82. Tsaytler P.; Harding H. P.; Ron D.; Bertolotti A. Selective inhibition of a regulatory subunit of protein phosphatase 1 restores pro-teostasis. Science, 2011, 332 (6025) 91-94.
83. Boyce M.; Bryant K. F.; Jousse C.; Long K.; Harding H. P.; Sche-uner D.; Kaufman R. J.; Ma D.; Coen D. M.; Ron D.; Yuan J. A selective inhibitor of eIF2alpha dephosphorylation protects cells from ER stress. Science, 2005, 307 (5711) 935-939.
84. Cross B. C.; Bond P. J.; Sadowski P. G.; Jha B. K.; Zak J.; Goodman J. M.; Silverman R. H.; Neubert T. A.; Baxendale I. R.; Ron D.; Harding H. P. The molecular basis for selective inhibition of unconventional mRNA splicing by an IRE1-binding small molecule. Proc. Natl. Acad. Sci. U. S. A., 2012, 109 (15) E869-E878.
85. Volkmann K.; Lucas J. L.; Vuga D.; Wang X.; Brumm D.; Stiles C.; Kriebel D.; Der-Sarkissian A.; Krishnan K.; Schweitzer C.; Liu Z.; Malyankar U. M.; Chiovitti D.; Canny M.; Durocher D.; Sicheri F.; Patterson J. B. Potent and selective inhibitors of the inositol-requiring enzyme 1 endoribonuclease. J. Biol. Chem., 2011, 286 (14) 12743-12755.
86. Papandreou I.; Denko N. C.; Olson M.; Van Melckebeke H.; Lust S.; Tam A.; Solow-Cordero D. E.; Bouley D. M.; Offner F.; Niwa M.; Koong A. C. Identification of an Ire1alpha endonuclease specific inhibitor with cytotoxic activity against human multiple myeloma. Blood, 2011, 117 (4) 1311-1314.
87. Lee A. H.; Chu G. C.; Iwakoshi N. N.; Glimcher L. H. XBP-1 is required for biogenesis of cellular secretory machinery of exocrine glands. EMBO J., 2005, 24 (24) 4368-4380.
88. Reimold A. M.; Iwakoshi N. N.; Manis J.; Vallabhajosyula P.; Szomolanyi-Tsuda E.; Gravallese E. M.; Friend D.; Grusby M. J.; Alt F.; Glimcher L. H. Plasma cell differentiation requires the transcription factor XBP-1. Nature, 2001, 412 (6844) 300-307.
89. Hess D. A.; Humphrey S. E.; Ishibashi J.; Damsz B.; Lee A. H.; Glimcher L. H.; Konieczny S. F. Extensive pancreas regeneration following acinar-specific disruption of Xbp1 in mice. Gastroen-terology, 2011, 141 (4) 1463-1472.
90. Reimold A. M.; Etkin A.; Clauss I.; Perkins A.; Friend D. S.; Zhang J.; Horton H. F.; Scott A.; Orkin S. H.; Byrne M. C.; Grusby M. J.; Glimcher L. H. An essential role in liver development for transcription factor XBP-1. Genes Dev., 2000, 14 (2) 152-157.
91. Zhang K.; Wong H. N.; Song B.; Miller C. N.; Scheuner D.; Kaufman R. J. The unfolded protein response sensor IRE1alpha is required at 2 distinct steps in B cell lymphopoiesis. J. Clin. Invest., 2005, 115 (2) 268-281.
92. Wang F.; Song W.; Brancati G.; Segatori L. Inhibition of endo-plasmic reticulum-associated degradation rescues native folding in loss of function protein misfolding diseases. J. Biol. Chem., 2011, 286 (50) 43454-43464.
93. Mizushima N.; Levine B.; Cuervo A. M.; Klionsky D. J. Auto-phagy fights disease through cellular self-digestion. Nature, 2008, 451 (7182) 1069-1075.
94. Ciechanover A.; Schwartz A. L. The ubiquitin-proteasome pathway: the complexity and myriad functions of proteins death. Proc. Natl. Acad. Sci. U. S. A., 1998, 95 (6) 2727-2730.
95. Hershko A. The ubiquitin system for protein degradation and some of its roles in the control of the cell division cycle. Cell Death Differ., 2005, 12 (9) 1191-1197.
96. Nalepa G.; Rolfe M.; Harper J. W. Drug discovery in the ubiquitin-proteasome system. Nat. Rev. Drug Discov., 2006, 5 (7) 596-613.
97. Sarkar S.; Rubinsztein D. C. Small molecule enhancers of auto-phagy for neurodegenerative diseases. Mol Biosyst, 2008, 4 (9) 895-901.
98. Adams J. The proteasome: structure function and role in the cell. Cancer Treat. Rev., 2003, 29 Suppl 13-19.
99. Weissman A. M.; Shabek N.; Ciechanover A. The predator becomes the prey: regulating the ubiquitin system by ubiquitylation and degradation. Nat. Rev. Mol. Cell Biol., 2011, 12 (9) 605-620.
100. Noda T.; Ohsumi Y. Tor a phosphatidylinositol kinase homologue controls autophagy in yeast. J. Biol. Chem., 1998, 273 (7) 3963-3966.
101. Hockerman G. H.; Peterson B. Z.; Johnson B. D.; Catterall W. A. Molecular determinants of drug binding and action on L-type calcium channels. Annual review of pharmacology and toxicology, 1997, 37361-37396.
102. Sarkar S.; Perlstein E. O.; Imarisio S.; Pineau S.; Cordenier A.; Maglathlin R. L.; Webster J. A.; Lewis T. A.; O'Kane C. J.; Schrei-ber S. L.; Rubinsztein D. C. Small molecules enhance autophagy and reduce toxicity in Huntington's disease models. Nat. Chem. Biol., 2007, 3 (6) 331-338.
103. Floto R. A.; Sarkar S.; Perlstein E. O.; Kampmann B.; Schreiber S. L.; Rubinsztein D. C. Small molecule enhancers of rapamycin-induced TOR inhibition promote autophagy reduce toxicity in Huntington's disease models and enhance killing of mycobacteria by macrophages. Autophagy, 2007, 3 (6) 620-622.
104. Tian Y.; Bustos V.; Flajolet M.; Greengard P. A small-molecule enhancer of autophagy decreases levels of Abeta and APP-CTF via Atg5-dependent autophagy pathway. FASEB J.2011, 25 (6), 1934-1942.
105. Zhang L.; Yu J.; Pan H.; Hu P.; Hao Y.; Cai W.; Zhu H.; Yu A. D.; Xie X.; Ma D.; Yuan J. Small molecule regulators of autophagy identified by an image-based high-throughput screen. Proc. Natl. Acad. Sci. U. S. A., 2007, 104 (48), 19023-19028.
106. Williams A.; Sarkar S.; Cuddon P.; Ttofi E. K.; Saiki S.; Siddiqi F. H.; Jahreiss L.; Fleming A.; Pask D.; Goldsmith P.; O'Kane C. J.; Floto R. A.; Rubinsztein D. C. Novel targets for Huntington's disease in an mTOR-independent autophagy pathway. Nat. Chem. Biol., 2008, 4 (5) 295-305.
107. Sarkar S.; Davies J. E.; Huang Z.; Tunnacliffe A.; Rubinsztein D. C. Trehalose a novel mTOR-independent autophagy enhancer accelerates the clearance of mutant huntingtin and alpha-synuclein. J. Biol. Chem., 2007, 282 (8) 5641-5652.
108. Komatsu M.; Waguri S.; Chiba T.; Murata S.; Iwata J.; Tanida I.; Ueno T.; Koike M.; Uchiyama Y.; Kominami E.; Tanaka K. Loss of autophagy in the central nervous system causes neurodegeneration in mice. Nature, 2006, 441 (7095) 880-884.
109. Hara T.; Nakamura K.; Matsui M.; Yamamoto A.; Nakahara Y.; Suzuki-Migishima R.; Yokoyama M.; Mishima K.; Saito I.; Okano H.; Mizushima N. Suppression of basal autophagy in neural cells causes neurodegenerative disease in mice. Nature, 2006, 441 (7095) 885-889.
110. Tsvetkov A. S.; Miller J.; Arrasate M.; Wong J. S.; Pleiss M. A.; Finkbeiner S. A small-molecule scaffold induces autophagy in primary neurons and protects against toxicity in a Huntington disease model. Proc. Natl. Acad. Sci. U. S. A., 2010, 107 (39) 16982-16987.
111. Perlmutter D. H. Alpha-1-antitrypsin deficiency: importance of proteasomal and autophagic degradative pathways in disposal of liver disease-associated protein aggregates. Annu. Rev. Med., 2011, 62 333-345.
112. Hidvegi T.; Ewing M.; Hale P.; Dippold C.; Beckett C.; Kemp C.; Maurice N.; Mukherjee A.; Goldbach C.; Watkins S.; Michalopou-los G.; Perlmutter D. H. An autophagy-enhancing drug promotes degradation of mutant alpha1-antitrypsin Z and reduces hepatic fi-brosis. Science, 2010, 329 (5988) 229-232.
113. Lee B. H.; Lee M. J.; Park S.; Oh D. C.; Elsasser S.; Chen P. C.; Gartner C.; Dimova N.; Hanna J.; Gygi S. P.; Wilson S. M.; King R. W.; Finley D. Enhancement of proteasome activity by a small-molecule inhibitor of USP14. Nature, 2010, 467 (7312) 179-184.
114. Berridge M. J.; Bootman M. D.; Lipp P. Calcium--a life and death signal. Nature, 1998, 395 (6703) 645-648.
115. Michalak M.; Robert Parker J. M.; Opas M. Ca2+ signaling and calcium binding chaperones of the endoplasmic reticulum. Cell Calcium, 2002, 32 (5-6) 269-278.
116. Egan M. E.; Glockner-Pagel J.; Ambrose C.; Cahill P. A.; Pappoe L.; Balamuth N.; Cho E.; Canny S.; Wagner C. A.; Geibel J.; Caplan M. J. Calcium-pump inhibitors induce functional surface expression of Delta F508-CFTR protein in cystic fibrosis epithelial cells. Nat. Med., 2002, 8 (5) 485-492.
117. Grubb B. R.; Gabriel S. E.; Mengos A.; Gentzsch M.; Randell S. H.; Van Heeckeren A. M.; Knowles M. R.; Drumm M. L.; Riordan J. R.; Boucher R. C. SERCA pump inhibitors do not correct bio-synthetic arrest of deltaF508 CFTR in cystic fibrosis. Am. J. Respir. Cell Mol. Biol., 2006, 34 (3) 355-363.
118. Loo T. W.; Bartlett M. C.; Clarke D. M. Thapsigargin or curcumin does not promote maturation of processing mutants of the ABC transporters CFTR and P-glycoprotein. Biochem. Biophys. Res. Commun., 2004, 325 (2) 580-585.
119. Egan M. E.; Pearson M.; Weiner S. A.; Rajendran V.; Rubin D.; Glockner-Pagel J.; Canny S.; Du K.; Lukacs G. L.; Caplan M. J. Curcumin a major constituent of turmeric corrects cystic fibrosis defects. Science, 2004, 304 (5670) 600-602.
120. Song Y.; Sonawane N. D.; Salinas D.; Qian L.; Pedemonte N.; Galietta L. J.; Verkman A. S. Evidence against the rescue of defective DeltaF508-CFTR cellular processing by curcumin in cell culture and mouse models. J. Biol. Chem., 2004, 279 (39) 40629-40633.
121. Dragomir A.; Bjorstad J.; Hjelte L.; Roomans G. M. Curcumin does not stimulate cAMP-mediated chloride transport in cystic fi-brosis airway epithelial cells. Biochem. Biophys. Res. Commun., 2004, 322 (2) 447-451.
122. Mall M.; Kunzelmann K. Correction of the CF defect by curcumin: hypes and disappointments. Bioessays, 2005, 27 (1) 9-13.
123. Wang F.; Agnello G.; Sotolongo N.; Segatori L. Ca2+ homeostasis modulation enhances the amenability of L444P glucosylcerebrosi-dase to proteostasis regulation in patient-derived fibroblasts. ACS Chem. Biol., 2011, 6 (2) 158-168.
124. Wang F.; Chou A.; Segatori L. Lacidipine remodels protein folding and Ca 2+ homeostasis in Gaucher's disease fibroblasts: a mechanism to rescue mutant glucocerebrosidase. Chem. Biol., 2011, 18 (6) 766-776.
125. Mu T. W.; Fowler D. M.; Kelly J. W. Partial restoration of mutant enzyme homeostasis in three distinct lysosomal storage disease cell lines by altering calcium homeostasis. PLoS Biol., 2008, 6 (2) e26.
126. Ong D. S.; Mu T. W.; Palmer A. E.; Kelly J. W. Endoplasmic reticulum Ca2+ increases enhance mutant glucocerebrosidase pro-teostasis. Nat. Chem. Biol., 2010, 6 (6) 424-432.
127. Westerheide S. D.; Anckar J.; Stevens S. M. Jr.; Sistonen L.; Mo-rimoto R. I. Stress-inducible regulation of heat shock factor 1 by the deacetylase SIRT1. Science, 2009, 323 (5917) 1063-1066.
128. Kazantsev A. G.; Thompson L. M. Therapeutic application of histone deacetylase inhibitors for central nervous system disorders. Nat. Rev. Drug Discov., 2008, 7 (10) 854-868.
129. Drummond D. C.; Noble C. O.; Kirpotin D. B.; Guo Z.; Scott G. K.; Benz C. C. Clinical development of histone deacetylase inhibitors as anticancer agents. Annu. Rev. Pharmacol. Toxicol., 2005, 45 495-528.
130. Fischer A.; Sananbenesi F.; Mungenast A.; Tsai L. H. Targeting the correct HDAC(s) to treat cognitive disorders. Trends Pharmacol. Sci., 2010, 31 (12) 605-617.
131. Hockerman G. H.; Peterson B. Z.; Sharp E.; Tanada T. N.; Scheuer T.; Catterall W. A. Construction of a high-affinity receptor site for dihydropyridine agonists and antagonists by single amino acid substitutions in a non-L-type Ca2+ channel. Proc. Natl. Acad. Sci. U. S. A., 1997, 94 (26) 14906-14911.
132. Ricobaraza A.; Cuadrado-Tejedor M.; Perez-Mediavilla A.; Fre-chilla D.; Del Rio J.; Garcia-Osta A. Phenylbutyrate ameliorates cognitive deficit and reduces tau pathology in an Alzheimer's disease mouse model. Neuropsychopharmacology, 2009, 34 (7) 1721-1732.
133. Fischer A.; Sananbenesi F.; Wang X.; Dobbin M.; Tsai L. H. Recovery of learning and memory is associated with chromatin remodelling. Nature, 2007, 447 (7141) 178-182.
134. Kilgore M.; Miller C. A.; Fass D. M.; Hennig K. M.; Haggarty S. J.; Sweatt J. D.; Rumbaugh G. Inhibitors of class 1 histone deacety-lases reverse contextual memory deficits in a mouse model of Alzheimer's disease. Neuropsychopharmacology, 2010, 35 (4) 870-880.
135. Lu J.; Yang C.; Chen M.; Ye D. Y.; Lonser R. R.; Brady R. O.; Zhuang Z. Histone deacetylase inhibitors prevent the degradation and restore the activity of glucocerebrosidase in Gaucher disease. Proc. Natl. Acad. Sci. U. S. A., 2011, 108 (52) 21200-21205.
136. Hutt D. M.; Herman D.; Rodrigues A. P.; Noel S.; Pilewski J. M.; Matteson J.; Hoch B.; Kellner W.; Kelly J. W.; Schmidt A.; Thomas P. J.; Matsumura Y.; Skach W. R.; Gentzsch M.; Riordan J. R.; Sorscher E. J.; Okiyoneda T.; Yates J. R. 3rd; Lukacs G. L.; Friz-zell R. A.; Manning G.; Gottesfeld J. M.; Balch W. E. Reduced his-tone deacetylase 7 activity restores function to misfolded CFTR in cystic fibrosis. Nat. Chem. Biol., 2010, 6 (1) 25-33.
137. Ozcan U.; Yilmaz E.; Ozcan L.; Furuhashi M.; Vaillancourt E.; Smith R. O.; Gorgun C. Z.; Hotamisligil G. S. Chemical chaper-ones reduce ER stress and restore glucose homeostasis in a mouse model of type 2 diabetes. Science, 2006, 313 (5790) 1137-1140.
138. Kovacs J. J.; Murphy P. J.; Gaillard S.; Zhao X.; Wu J. T.; Nic-chitta C. V.; Yoshida M.; Toft D. O.; Pratt W. B.; Yao T. P. HDAC6 regulates Hsp90 acetylation and chaperone-dependent activation of glucocorticoid receptor. Mol. Cell, 2005, 18 (5) 601-607.
139. Marks P. A.; Breslow R. Dimethyl sulfoxide to vorinostat: development of this histone deacetylase inhibitor as an anticancer drug. Nat. Biotechnol., 2007, 25 (1) 84-90.
140. Ramalingam S. S.; Parise R. A.; Ramanathan R. K.; Lagattuta T. F.; Musguire L. A.; Stoller R. G.; Potter D. M.; Argiris A. E.; Zwiebel J. A.; Egorin M. J.; Belani C. P. Phase I and pharmacoki-netic study of vorinostat a histone deacetylase inhibitor in combination with carboplatin and paclitaxel for advanced solid malignancies. Clin. Cancer. Res., 2007, 13 (12) 3605-3610.
141. Bukau B.; Weissman J.; Horwich A. Molecular chaperones and protein quality control. Cell, 2006, 125 (3) 443-451.
142. Liberek K.; Lewandowska A.; Zietkiewicz S. Chaperones in control of protein disaggregation. EMBO J., 2008, 27 (2) 328-335.
143. Wickner S.; Hoskins J.; McKenney K. Function of DnaJ and DnaK as chaperones in origin-specific DNA binding by RepA. Nature, 1991, 350 (6314) 165-167.
144. Langer T.; Lu C.; Echols H.; Flanagan J.; Hayer M. K.; Hartl F. U. Successive action of DnaK DnaJ and GroEL along the pathway of chaperone-mediated protein folding. Nature, 1992, 356 (6371) 683-689.
145. Szabo A.; Langer T.; Schroder 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. U. S. A., 1994, 91 (22) 10345-10349.
146. Gamer J.; Multhaup G.; Tomoyasu T.; McCarty J. S.; Rudiger S.; Schonfeld H. J.; Schirra C.; Bujard H.; Bukau B. A cycle of binding and release of the DnaK DnaJ and GrpE chaperones regulates activity of the Escherichia coli heat shock transcription factor sigma32. EMBO J., 1996, 15 (3) 607-617.
147. Laufen T.; Mayer M. P.; Beisel C.; Klostermeier D.; Mogk A.; Reinstein J.; Bukau B. Mechanism of regulation of hsp70 chaper-ones by DnaJ cochaperones. Proc. Natl. Acad. Sci. U. S. A., 1999, 96 (10) 5452-5457.
148. Han W.; Christen P. Mechanism of the targeting action of DnaJ in the DnaK molecular chaperone system. J. Biol. Chem., 2003, 278 (21), 19038-19043.
149. Misselwitz B.; Staeck O.; Rapoport T. A. J proteins catalytically activate Hsp70 molecules to trap a wide range of peptide sequences. Mol. Cell, 1998, 2 (5) 593-603.
150. Nadler S. G.; Tepper M. A.; Schacter B.; Mazzucco C. E. Interaction of the immunosuppressant deoxyspergualin with a member of the Hsp70 family of heat shock proteins. Science, 1992, 258 (5081) 484-486.
151. Nadeau K.; Nadler S. G.; Saulnier M.; Tepper M. A.; Walsh C. T. Quantitation of the interaction of the immunosuppressant deox-yspergualin and analogs with Hsc70 and Hsp90. Biochemistry, 1994, 33 (9) 2561-2567.
152. Jiang C.; Fang S. L.; Xiao Y. F.; O'Connor S. P.; Nadler S. G.; Lee D. W.; Jefferson D. M.; Kaplan J. M.; Smith A. E.; Cheng S. H. Partial restoration of cAMP-stimulated CFTR chloride channel activity in DeltaF508 cells by deoxyspergualin. Am. J. Physiol., 1998, 275 (1 Pt 1) C171-C178.
153. Fewell S. W.; Smith C. M.; Lyon M. A.; Dumitrescu T. P.; Wipf P.; Day B. W.; Brodsky J. L. Small molecule modulators of endogenous and co-chaperone-stimulated Hsp70 ATPase activity. J. Biol. Chem., 2004, 279 (49) 51131-51140.
154. Mamelak D.; Lingwood C. The ATPase domain of hsp70 possesses a unique binding specificity for 3'-sulfogalactolipids. J. Biol. Chem., 2001, 276 (1) 449-456.
155. Whetstone H.; Lingwood C. 3'Sulfogalactolipid binding specifically inhibits Hsp70 ATPase activity in vitro. Biochemistry, 2003, 42 (6) 1611-1617.
156. Chang L.; Bertelsen E. B.; Wisen S.; Larsen E. M.; Zuiderweg E. R.; Gestwicki J. E. High-throughput screen for small molecules that modulate the ATPase activity of the molecular chaperone DnaK. Anal. Biochem., 2008, 372 (2) 167-176.
157. Jinwal U. K.; Miyata Y.; Koren J. 3rd; Jones J. R.; Trotter J. H.; Chang L.; O'Leary J.; Morgan D.; Lee D. C.; Shults C. L.; Rousaki A.; Weeber E. J.; Zuiderweg E. R.; Gestwicki J. E.; Dickey C. A. Chemical manipulation of hsp70 ATPase activity regulates tau stability. J. Neurosci., 2009, 29 (39) 12079-12088.
158. Rafii M. S.; Aisen P. S. Recent developments in Alzheimer's disease therapeutics. BMC Med., 2009, 77.
159. Chang L.; Miyata Y.; Ung P. M.; Bertelsen E. B.; McQuade T. J.; Carlson H. A.; Zuiderweg E. R.; Gestwicki J. E. Chemical screens against a reconstituted multiprotein complex: myricetin blocks DnaJ regulation of DnaK through an allosteric mechanism. Chem. Biol., 2011, 18 (2) 210-221.
160. Wisen S.; Bertelsen E. B.; Thompson A. D.; Patury S.; Ung P.; Chang L.; Evans C. G.; Walter G. M.; Wipf P.; Carlson H. A.; Brodsky J. L.; Zuiderweg E. R.; Gestwicki J. E. Binding of a small molecule at a protein-protein interface regulates the chaperone activity of hsp70-hsp40. ACS Chem. Biol., 2010, 5 (6) 611-622.
161. Johnson S. M.; Connelly S.; Fearns C.; Powers E. T.; Kelly J. W. The transthyretin amyloidoses: from delineating the molecular mechanism of aggregation linked to pathology to a regulatory-agency-approved drug. J. Mol. Biol., 2012 421 (2-3) 185-203.
162. Asano N.; Ishii S.; Kizu H.; Ikeda K.; Yasuda K.; Kato A.; Martin O. R.; Fan J. Q. In vitro inhibition and intracellular enhancement of lysosomal alpha-galactosidase A activity in Fabry lymphoblasts by 1-deoxygalactonojirimycin and its derivatives. Eur. J. Biochem., 2000, 267 (13) 4179-4186.
163. Dai C.; Whitesell L.; Rogers A. B.; Lindquist S. Heat shock factor 1 is a powerful multifaceted modifier of carcinogenesis. Cell, 2007, 130 (6) 1005-1018.
164. Mendillo M. L.; Santagata S.; Koeva M.; Bell G. W.; Hu R.; Tamimi R. M.; Fraenkel E.; Ince T. A.; Whitesell L.; Lindquist S. HSF1 drives a transcriptional program distinct from heat shock to support highly malignant human cancers. Cell, 2012, 150 (3) 549-562.