Druggable sensors of the unfolded protein response

Nature Chemical Biology

Volumn 10, Issue 11, 2014, Pages 892-901

  Maly, Dustin J ^a   Papa, Feroz R ^b,c,d  

^a UNIVERSITY OF WASHINGTON   (United States)

^b UNIVERSITY OF CALIFORNIA   (United States)

^c UNIVERSITY OF CALIFORNIA   (United States)

^d UNIVERSITY OF CALIFORNIA   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

INOSITOL; INOSITOL REQUIRING ENZYME 1 ALPHA; PANCREATIC ER KINASE; PHOSPHOTRANSFERASE; UNCLASSIFIED DRUG; PERK KINASE; PROTEIN KINASE R; PROTEIN SERINE THREONINE KINASE; RIBONUCLEASE;

APOPTOSIS; ENDOPLASMIC RETICULUM STRESS; HOMEOSTASIS; HUMAN; INTRACELLULAR SIGNALING; NONHUMAN; PATHOGENESIS; PRIORITY JOURNAL; REVIEW; RNA TRANSLATION; SENSOR; UNFOLDED PROTEIN RESPONSE; ANIMAL; CHEMISTRY; DRUG EFFECTS; ENDOPLASMIC RETICULUM; ENZYMOLOGY; GENETICS; METABOLISM; SIGNAL TRANSDUCTION;

ANIMALS; EIF-2 KINASE; ENDOPLASMIC RETICULUM; ENDOPLASMIC RETICULUM STRESS; ENDORIBONUCLEASES; HOMEOSTASIS; HUMANS; PROTEIN-SERINE-THREONINE KINASES; SIGNAL TRANSDUCTION; UNFOLDED PROTEIN RESPONSE;

EID: 84921403151     PISSN: 15524450     EISSN: 15524469     Source Type: Journal    
DOI: 10.1038/NCHEMBIO.1664     Document Type: Review

References (101)

1. Anelli, T. & Sitia, R. Protein quality control in the early secretory pathway. EMBO J. 27, 315-327 (2008)
2. Tu, B.P. & Weissman, J.S. Oxidative protein folding in eukaryotes: mechanisms and consequences. J. Cell Biol. 164, 341-346 (2004)
3. Sevier, C.S. & Kaiser, C.A. Formation and transfer of disulphide bonds in living cells. Nat. Rev. Mol. Cell Biol. 3, 836-847 (2002)
4. van Anken, E. & Braakman, I. Versatility of the endoplasmic reticulum protein folding factory. Crit. Rev. Biochem. Mol. Biol. 40, 191-228 (2005)
5. Merksamer, P.I., Trusina, A. & Papa, F.R. Real-time redox measurements during endoplasmic reticulum stress reveal interlinked protein folding functions. Cell 135, 933-947 (2008)
6. Smith, M.H., Ploegh, H.L. & Weissman, J.S. Road to ruin: targeting proteins for degradation in the endoplasmic reticulum. Science 334, 1086-1090 (2011)
7. Meusser, B., Hirsch, C., Jarosch, E. & Sommer, T. ERAD: the long road to destruction. Nat. Cell Biol. 7, 766-772 (2005)
8. Scheuner, D. & Kaufman, R.J. The unfolded protein response: a pathway that links insulin demand with b-cell failure and diabetes. Endocr. Rev. 29, 317-333 (2008)
9. van Anken, E. et al. Efficient IgM assembly and secretion require the plasma cell induced endoplasmic reticulum protein pERp1. Proc. Natl. Acad. Sci. USA 106, 17019-17024 (2009)
10. Tabas, I. & Ron, D. Integrating the mechanisms of apoptosis induced by endoplasmic reticulum stress. Nat. Cell Biol. 13, 184-190 (2011)
11. Oyadomari, S. et al. Targeted disruption of the Chop gene delays endoplasmic reticulum stress-mediated diabetes. J. Clin. Invest. 109, 525-532 (2002)
12. Zhang, H.M. et al. Coxsackievirus B3 infection activates the unfolded protein response and induces apoptosis through downregulation of p58IPK and activation of CHOP and SREBP1. J. Virol. 84, 8446-8459 (2010)
13. Ma, Y. & Hendershot, L.M. ER chaperone functions during normal and stress conditions. J. Chem. Neuroanat. 28, 51-65 (2004)
14. Flamment, M., Hajduch, E., Ferre, P. & Foufelle, F. New insights into ER stress-induced insulin resistance. Trends Endocrinol. Metab. 23, 381-390 (2012)
15. Gestwicki, J.E. & Garza, D. Protein quality control in neurodegenerative disease. Prog. Mol. Biol. Transl. Sci. 107, 327-353 (2012)
16. Wang, S. & Kaufman, R.J. The impact of the unfolded protein response on human disease. J. Cell Biol. 197, 857-867 (2012)
17. Pincus, D. et al. BiP binding to the ER-stress sensor Ire1 tunes the homeostatic behavior of the unfolded protein response. PLoS Biol. 8, e1000415 (2010)
18. Gardner, B.M. & Walter, P. Unfolded proteins are Ire1-activating ligands that directly induce the unfolded protein response. Science 333, 1891-1894 (2011)
19. Credle, J.J., Finer-Moore, J.S. & Papa, F.R. Stroud, R. M. & Walter, P. On the mechanism of sensing unfolded protein in the endoplasmic reticulum. Proc. Natl. Acad. Sci. USA 102, 18773-18784 (2005)
20. Walter, P. & Ron, D. The unfolded protein response: from stress pathway to homeostatic regulation. Science 334, 1081-1086 (2011)
21. Travers, K.J. et al. Functional and genomic analyses reveal an essential coordination between the unfolded protein response and ER-associated degradation. Cell 101, 249-258 (2000)
22. Harding, H.P., Zhang, Y. & Ron, D. Protein translation and folding are coupled by an endoplasmic-reticulum-resident kinase. Nature 397, 271-274 (1999)
23. Tirasophon, W., Welihinda, A.A. & Kaufman, R.J. A stress response pathway from the endoplasmic reticulum to the nucleus requires a novel bifunctional protein kinase/endoribonuclease (Ire1p) in mammalian cells. Genes Dev. 12, 1812-1824 (1998)
24. Wang, X.Z. et al. Cloning of mammalian Ire1 reveals diversity in the ER stress responses. EMBO J. 17, 5708-5717 (1998)
25. Korennykh, A. & Walter, P. Structural basis of the unfolded protein response. Annu. Rev. Cell Dev. Biol. 28, 251-277 (2012)
26. Calfon, M. et al. IRE1 couples endoplasmic reticulum load to secretory capacity by processing the XBP-1 mRNA. Nature 415, 92-96 (2002)
27. Yoshida, H., Matsui, T., Yamamoto, A., Okada, T. & Mori, K. XBP1 mRNA is induced by ATF6 and spliced by IRE1 in response to ER stress to produce a highly active transcription factor. Cell 107, 881-891 (2001)
28. Yamamoto, K. et al. Transcriptional induction of mammalian ER quality control proteins is mediated by single or combined action of ATF6a and XBP1. Dev. Cell 13, 365-376 (2007)
29. Liu, C.Y., Schroder, M. & Kaufman, R.J. Ligand-independent dimerization activates the stress response kinases IRE1 and PERK in the lumen of the endoplasmic reticulum. J. Biol. Chem. 275, 24881-24885 (2000)
30. Bertolotti, A., Zhang, Y., Hendershot, L.M., Harding, H.P. & Ron, D. Dynamic interaction of BiP and ER stress transducers in the unfolded-protein response. Nat. Cell Biol. 2, 326-332 (2000)
31. Harding, H.P. et al. An integrated stress response regulates amino acid metabolism and resistance to oxidative stress. Mol. Cell 11, 619-633 (2003)
32. Ye, J. et al. ER stress induces cleavage of membrane-bound ATF6 by the same proteases that process SREBPs. Mol. Cell 6, 1355-1364 (2000)
33. Lee, K.P. et al. Structure of the dual enzyme Ire1 reveals the basis for catalysis and regulation in nonconventional RNA splicing. Cell 132, 89-100 (2008)
34. Wang, L. et al. Divergent allosteric control of the IRE1a endoribonuclease using kinase inhibitors. Nat. Chem. Biol. 8, 982-989 (2012)
35. Korennykh, A.V. et al. The unfolded protein response signals through high-order assembly of Ire1. Nature 457, 687-693 (2009)
36. Korennykh, A.V. et al. Cofactor-mediated conformational control in the bifunctional kinase/RNase Ire1. BMC Biol. 9, 48 (2011)
37. Ali, M.M. et al. Structure of the Ire1 autophosphorylation complex and implications for the unfolded protein response. EMBO J. 30, 894-905 (2011)
38. Shore, G.C., Papa, F.R. & Oakes, S.A. Signaling cell death from the endoplasmic reticulum stress response. Curr. Opin. Cell Biol. 23, 143-149 (2011)
39. Lu, P.D. et al. Cytoprotection by pre-emptive conditional phosphorylation of translation initiation factor 2. EMBO J. 23, 169-179 (2004)
40. Lin, J.H., Li, H., Zhang, Y., Ron, D. & Walter, P. Divergent effects of PERK and IRE1 signaling on cell viability. PLoS ONE 4, e4170 (2009)
41. McCullough, K.D., Martindale, J.L., Klotz, L.O., Aw, T.Y. & Holbrook, N.J. Gadd153 sensitizes cells to endoplasmic reticulum stress by down-regulating Bcl2 and perturbing the cellular redox state. Mol. Cell. Biol. 21, 1249-1259 (2001)
42. Marciniak, S.J. et al. CHOP induces death by promoting protein synthesis and oxidation in the stressed endoplasmic reticulum. Genes Dev. 18, 3066-3077 (2004)
43. Han, D. et al. IRE1a kinase activation modes control alternate endoribonuclease outputs to determine divergent cell fates. Cell 138, 562-575 (2009)
44. Hollien, J. & Weissman, J.S. Decay of endoplasmic reticulum-localized mRNAs during the unfolded protein response. Science 313, 104-107 (2006)
45. Han, D. et al. A kinase inhibitor activates the IRE1a RNase to confer cytoprotection against ER stress. Biochem. Biophys. Res. Commun. 365, 777-783 (2008)
46. Lin, J.H. et al. IRE1 signaling affects cell fate during the unfolded protein response. Science 318, 944-949 (2007)
47. Papa, F.R., Zhang, C., Shokat, K. & Walter, P. Bypassing a kinase activity with an ATP-competitive drug. Science 302, 1533-1537 (2003)
48. Upton, J.P. et al. IRE1a cleaves select microRNAs during ER stress to derepress translation of proapoptotic Caspase-2. Science 338, 818-822 (2012)
49. Lerner, A.G. et al. IRE1a induces thioredoxin-interacting protein to activate the NLRP3 inflammasome and promote programmed cell death under irremediable ER stress. Cell Metab. 16, 250-264 (2012)
50. Urano, F. et al. Coupling of stress in the ER to activation of JNK protein kinases by transmembrane protein kinase IRE1. Science 287, 664-666 (2000)
51. Nishitoh, H. et al. ASK1 is essential for endoplasmic reticulum stress-induced neuronal cell death triggered by expanded polyglutamine repeats. Genes Dev. 16, 1345-1355 (2002)
52. Wang, C. & Youle, R.J. The role of mitochondria in apoptosis. Annu. Rev. Genet. 43, 95-118 (2009)
53. Chipuk, J.E., Moldoveanu, T., Llambi, F., Parsons, M.J. & Green, D.R. The BCL-2 family reunion. Mol. Cell 37, 299-310 (2010)
54. Giam, M., Huang, D.C. & Bouillet, P. BH3-only proteins and their roles in programmed cell death. Oncogene 27, Suppl 1, S128-S136 (2008)
55. Upton, J.P. et al. Caspase-2 cleavage of BID is a critical apoptotic signal downstream of endoplasmic reticulum stress. Mol. Cell. Biol. 28, 3943-3951 (2008)
56. Puthalakath, H. et al. ER stress triggers apoptosis by activating BH3-only protein Bim. Cell 129, 1337-1349 (2007)
57. Li, J., Lee, B. & Lee, A.S. Endoplasmic reticulum stress-induced apoptosis: multiple pathways and activation of p53-up-regulated modulator of apoptosis (PUMA) and NOXA by p53. J. Biol. Chem. 281, 7260-7270 (2006)
58. Papa, F.R. Endoplasmic reticulum stress, pancreatic b-cell degeneration, and diabetes. Cold Spring Harb. Perspect. Med. 2, a007666 (2012)
59. Iwawaki, T., Akai, R., Kohno, K. & Miura, M. A transgenic mouse model for monitoring endoplasmic reticulum stress. Nat. Med. 10, 98-102 (2004)
60. Harding, H.P., Zhang, Y., Bertolotti, A., Zeng, H. & Ron, D. Perk is essential for translational regulation and cell survival during the unfolded protein response. Mol. Cell 5, 897-904 (2000)
61. Delépine, M. et al. EIF2AK3, encoding translation initiation factor 2 - a kinase 3, is mutated in patients with Wolcott-Rallison syndrome. Nat. Genet. 25, 406-409 (2000)
62. Reimold, A.M. et al. Plasma cell differentiation requires the transcription factor XBP-1. Nature 412, 300-307 (2001)
63. Zhang, K. et al. The unfolded protein response sensor IRE1a is required at 2 distinct steps in B cell lymphopoiesis. J. Clin. Invest. 115, 268-281 (2005)
64. Lee, A.H., Heidtman, K., Hotamisligil, G.S. & Glimcher, L.H. Dual and opposing roles of the unfolded protein response regulated by IRE1a and XBP1 in proinsulin processing and insulin secretion. Proc. Natl. Acad. Sci. USA 108, 8885 (2011)
65. Harding, H.P. et al. Diabetes mellitus and exocrine pancreatic dysfunction in Perk mice reveals a role for translational control in secretory cell survival. Mol. Cell 7, 1153-1163 (2001)
66. Ross, C.A. & Poirier, M.A. Protein aggregation and neurodegenerative disease. Nat. Med. 10, S10-S17 (2004)
67. Taylor, J.P. J.P., Hardy, J. & Fischbeck, K.H. Toxic proteins in neurodegenerative disease. Science 296, 1991-1995 (1991).
68. Roussel, B.D. et al. Endoplasmic reticulum dysfunction in neurological disease. Lancet Neurol. 12, 105-118 (2013)
69. Hamos, J.E. et al. Expression of heat shock proteins in Alzheimer's disease. Neurology 41, 345-350 (1991)
70. Hoozemans, J.J. et al. The unfolded protein response is activated in pretangle neurons in Alzheimer's disease hippocampus. Am. J. Pathol. 174, 1241-1251 (2009)
71. Unterberger, U. et al. Endoplasmic reticulum stress features are prominent in Alzheimer disease but not in prion diseases in vivo. J. Neuropathol. Exp. Neurol. 65, 348-357 (2006)
72. Wang, H.Q. & Takahashi, R. Expanding insights on the involvement of endoplasmic reticulum stress in Parkinson's disease. Antioxid. Redox Signal. 9, 553-561 (2007)
73. Atkin, J.D. et al. Endoplasmic reticulum stress and induction of the unfolded protein response in human sporadic amyotrophic lateral sclerosis. Neurobiol. Dis. 30, 400-407 (2008)
74. Holtz, W.A. & O'Malley, K.L. Parkinsonian mimetics induce aspects of unfolded protein response in death of dopaminergic neurons. J. Biol. Chem. 278, 19367-19377 (2003)
75. Atkin, J.D. et al. Induction of the unfolded protein response in familial amyotrophic lateral sclerosis and association of protein-disulfide isomerase with superoxide dismutase 1. J. Biol. Chem. 281, 30152-30165 (2006)
76. Kikuchi, H. et al. Spinal cord endoplasmic reticulum stress associated with a microsomal accumulation of mutant superoxide dismutase-1 in an ALS model. Proc. Natl. Acad. Sci. USA 103, 6025-6030 (2006)
77. Nishitoh, H. et al. ALS-linked mutant SOD1 induces ER stress-and ASK1-dependent motor neuron death by targeting Derlin-1. Genes Dev. 22, 1451-1464 (2008)
78. Moreno, J. A. et al. Oral treatment targeting the unfolded protein response prevents neurodegeneration and clinical disease in prion-infected mice. Sci. Transl. Med. 5, 206ra138 (2013).
79. Lee, A.S. & Hendershot, L.M. ER stress and cancer. Cancer Biol. Ther. 5, 721-722 (2006)
80. Koumenis, C. ER stress, hypoxia tolerance and tumor progression. Curr. Mol. Med. 6, 55-69 (2006)
81. Moenner, M., Pluquet, O., Bouchecareilh, M. & Chevet, E. Integrated endoplasmic reticulum stress responses in cancer. Cancer Res. 67, 10631-10634 (2007)
82. Carrasco, D.R. et al. The differentiation and stress response factor XBP-1 drives multiple myeloma pathogenesis. Cancer Cell 11, 349-360 (2007)
83. Fernandez, P.M. et al. Overexpression of the glucose-regulated stress gene GRP78 in malignant but not benign human breast lesions. Breast Cancer Res. Treat. 59, 15-26 (2000)
84. Shuda, M. et al. Activation of the ATF6, XBP1 and grp78 genes in human hepatocellular carcinoma: a possible involvement of the ER stress pathway in hepatocarcinogenesis. J. Hepatol. 38, 605-614 (2003)
85. Song, M.S., Park, Y.K., Lee, J.H. & Park, K. Induction of glucose-regulated protein 78 by chronic hypoxia in human gastric tumor cells through a protein kinase C-e/ERK/AP-1 signaling cascade. Cancer Res. 61, 8322-8330 (2001).
86. Chen, X., Ding, Y., Liu, C.G., Mikhail, S. & Yang, C.S. Overexpression of glucose-regulated protein 94 (Grp94) in esophageal adenocarcinomas of a rat surgical model and humans. Carcinogenesis 23, 123-130 (2002)
87. Greenman, C. et al. Patterns of somatic mutation in human cancer genomes. Nature 446, 153-158 (2007)
88. Chen, X. et al. XBP1 promotes triple-negative breast cancer by controlling the HIF1a pathway. Nature 508, 103-107 (2014)
89. Voorhees, P.M. & Orlowski, R.Z. The proteasome and proteasome inhibitors in cancer therapy. Annu. Rev. Pharmacol. Toxicol. 46, 189-213 (2006)
90. Papandreou, I. et al. Identification of an Ire1a endonuclease specific inhibitor with cytotoxic activity against human multiple myeloma. Blood 117, 1311-1314 (2011)
91. Mimura, N. et al. Blockade of XBP1 splicing by inhibition of IRE1a is a promising therapeutic option in multiple myeloma. Blood 119, 5772-5781 (2012)
92. Gu, J.L. et al. Differentiation induction enhances bortezomib efficacy and overcomes drug resistance in multiple myeloma. Biochem. Biophys. Res. Commun. 420, 644-650 (2012)
93. Ling, S.C. et al. Response of myeloma to the proteasome inhibitor bortezomib is correlated with the unfolded protein response regulator XBP-1. Haematologica 97, 64-72 (2012)
94. Chapman, M.A. et al. Initial genome sequencing and analysis of multiple myeloma. Nature 471, 467-472 (2011)
95. Ghosh, R. et al. Allosteric inhibition of the IRE1a RNase preserves cell viability and function during endoplasmic reticulum stress. Cell 158, 534-548 (2014)
96. Leung-Hagesteijn, C. et al. Xbp1s-negative tumor B cells and pre-plasmablasts mediate therapeutic proteasome inhibitor resistance in multiple myeloma. Cancer Cell 24, 289-304 (2013)
97. Boyce, M. et al. A selective inhibitor of eIF2a dephosphorylation protects cells from ER stress. Science 307, 935-939 (2005)
98. Atkins, C. et al. Characterization of a novel PERK kinase inhibitor with antitumor and antiangiogenic activity. Cancer Res. 73, 1993-2002 (2013)
99. Volkmann, K. et al. Potent and selective inhibitors of the inositol-requiring enzyme 1 endoribonuclease. J. Biol. Chem. 286, 12743-12755 (2011)
100. Cross, B.C. et al. The molecular basis for selective inhibition of unconventional mRNA splicing by an IRE1-binding small molecule. Proc. Natl. Acad. Sci. USA 109, E869-E878 (2012)
101. Sanches, M. et al. Structure and mechanism of action of the hydroxy-aryl-aldehyde class of IRE1 endoribonuclease inhibitors. Nat. Commun. 5, 4202 (2014)