Cellular response to endoplasmic reticulum stress: A matter of life or death

Cell Death and Differentiation

Volumn 13, Issue 3, 2006, Pages 363-373

  Boyce, M ^a   Yuan, J ^a  

^a HARVARD MEDICAL SCHOOL   (United States)

Author keywords

Apoptosis; Endoplasmic reticulum; ER stress response; ER associated degradation; Translational control; Unfolded protein response

Indexed keywords

ACTIVATING TRANSCRIPTION FACTOR 4; ACTIVATING TRANSCRIPTION FACTOR 6; CASPASE 12; GROWTH ARREST AND DNA DAMAGE INDUCIBLE PROTEIN 153; MEMBRANE PROTEIN; PROTEIN BAK; PROTEIN BAX; PROTEIN BCL 2; PROTEIN BCL XL; PROTEIN IRE1; TRANSCRIPTION FACTOR; TRANSCRIPTION FACTOR ELF 2 ALPHA; TRANSCRIPTION FACTOR NRF2; TRANSCRIPTION FACTOR XBP 1; UNCLASSIFIED DRUG;

APOPTOSIS; CELL DEATH; CELL DIFFERENTIATION; CELL FUNCTION; ENDOPLASMIC RETICULUM; EUKARYOTE; HOMEOSTASIS; MAMMAL; METAZOON; MOLECULAR MECHANICS; NONHUMAN; PATHOGENESIS; PATHOPHYSIOLOGY; PRIORITY JOURNAL; PROTEIN ANALYSIS; PROTEIN DEGRADATION; PROTEIN FOLDING; PROTEIN FUNCTION; PROTEIN PROCESSING; REVIEW; STRESS; SYSTEMATIC REVIEW; YEAST;

ANIMALS; APOPTOSIS; ENDOPLASMIC RETICULUM; MAMMALS; SACCHAROMYCES CEREVISIAE; SIGNAL TRANSDUCTION;

EUKARYOTA; MAMMALIA; METAZOA;

EID: 33645154135     PISSN: 13509047     EISSN: 14765403     Source Type: Journal    
DOI: 10.1038/sj.cdd.4401817     Document Type: Review

References (173)

1. Alberts B, Johnson A, Lewis J, Raff M, Roberts K and Walter P (2002) Molecular Biology of the Cell (New York: Garland Publishing)
2. Kaufman RJ (1999) Stress signaling from the lumen of the endoplasmic reticulum: Coordination of gene transcriptional and translational controls. Genes Dev. 13: 1211-1233
3. Mori K (2000) Tripartite management of unfolded proteins in the endoplasmic reticulum. Cell 101: 451-454
4. Ma Y and Hendershot LM (2001) The unfolding tale of the unfolded protein response. Cell 107: 827-830
5. Schroder M and Kaufman RJ (2005) ER stress and the unfolded protein response. Mutat. Res. 569: 29-63
6. Schroder M and Kaufman RJ (2005) The Mammalian unfolded protein response. Annu. Rev. Biochem. 74: 739-789
7. Rutkowski DT and Kaufman RJ (2004) A trip to the ER: Coping with stress. Trends Cell Biol. 14: 20-28
8. Tsai B, Ye Y and Rapoport TA (2002) Retro-translocation of proteins from the endoplasmic reticulum into the cytosol. Nat. Rev. Mol. Cell. Biol. 3: 246-255
9. Jarosch E, Lank U and Sommer T (2003) Endoplasmic reticulum-associated protein degradation. Int. Rev. Cytol. 223: 39-81
10. Hampton RY (2002) ER-associated degradation in protein quality control and cellular regulation. Curr. Opin. Cell Biol. 14: 476-482
11. Plemper RK and Wolf DH (1999) Retrograde protein translocation: ERADication of secretory proteins in health and disease. Trends Biochem. Sci. 24: 266-270
12. Brostrom CO and Brostrom MA (1998) Regulation of translational initiation during cellular responses to stress. Prog. Nucleic Acid. Res. Mol. Biol. 58: 79-125
13. Harding HP, Calfon M, Urano F, Novoa I and Ron D (2002) Transcriptional and translational control in the Mammalian unfolded protein response. Annu. Rev. Cell Dev. Biol. 18: 575-599
14. Ferri KF and Kroemer G (2001) Organelle-specific initiation of cell death pathways. Nat. Cell Biol. 3: E255-E263
15. Rao RV, Ellerby HM and Bredesen DE (2004) Coupling endoplasmic reticulum stress to the cell death program. Cell Death Differ 11: 372-380
16. Breckenridge DG, Germain M, Mathai JP, Nguyen M and Shore GC (2003) Regulation of apoptosis by endoplasmic reticulum pathways. Oncogene 22: 8608-8618
17. Aridor M and Balch WE (1999) Integration of endoplasmic reticulum signaling in health and disease. Nat. Med. 5: 745-751
18. Paschen W (2003) Endoplasmic reticulum: A primary target in various acute disorders and degenerative diseases of the brain. Cell Calcium 34: 365-383
19. Rutishauser J and Spiess M (2002) Endoplasmic reticulum storage diseases. Swiss Med. Wkly. 132: 211-222
20. Aridor M and Hannan LA (2000) Traffic jam: A compendium of human diseases that affect intracellular transport processes. Traffic 1: 836-851
21. Aridor M and Hannan LA (2002) Traffic jams II: An update of diseases of intracellular transport. Traffic 3: 781-790
22. Patil C and Walter P (2001) Intracellular signaling from the endoplasmic reticulum to the nucleus: The unfolded protein response in yeast and mammals. Curr. Opin. Cell Biol. 13: 349-355
23. Shamu CE and Walter P (1996) Oligomerizabon and phosphorylation of the Ire1p kinase during intracellular signaling from the endoplasmic reticulum to the nucleus. EMBO J. 15: 3028-3039
24. Welihinda AA and Kaufman RJ (1996) The unfolded protein response pathway in Saccharomyces cerevisiae. Oligomerization and transphosphorylation of Ire1p (Em1p) are required for kinase activation. J. Biol. Chem. 271: 18181-18187
25. Bertolotti A, Zhang Y, Hendershot LM, Harding HP and Ron D (2000) Dynamic interaction of BiP and ER stress transducers in the unfolded-protein response. Nat. Cell Biol. 2: 326-332
26. Cox JS and Walter P (1996) A novel mechanism for regulating activity of a transcription factor that controls the unfolded protein response. Cell 87: 391-404
27. Mori K, Kawahara T, Yoshida H, Yanagi H and Yura T (1996) Signalling from endoplasmic reticulum to nucleus: Transcription factor with a basic-leucine zipper motif is required for the unfolded protein-response pathway. Genes Cells 1: 803-817
28. Chapman RE and Walter P (1997) Translational attenuation mediated by an mRNA intron. Curr. Biol. 7: 850-859
29. Kawahara T, Yanagi H, Yura T and Mori K (1997) Endoplasmic reticulum stress-induced mRNA splicing permits synthesis of transcription factor Hac1p/Em4p that activates the unfolded protein response. Mol. Biol. Cell 8: 1845-1862
30. Sidrauski C, Cox JS and Walter P (1996) tRNA ligase is required for regulated mRNA splicing in the unfolded protein response. Cell 87: 405-413
31. Mori K, Ogawa N, Kawahara T, Yanagi H and Yura T (2000) mRNA splicing-mediated C-terminal replacement of transcription factor Hac1p is required for efficient activation of the unfolded protein response. Proc. Natl. Acad. Sci. USA 97: 4660-4665
32. Travers KJ, Patil CK, Wodicka L, Lockhart DJ, Weissman JS and Walter P (2000) Functional and genomic analyses reveal an essential coordination between the unfolded protein response and ER-associated degradation. Cell 101: 249-258
33. Casagrande R, Stern P, Diehn M, Shamu C, Osario M, Zuniga M, Brown PO and Ploegh H (2000) Degradation of proteins from the ER of S. cerevisiae requires an intact unfolded protein response pathway. Mol. Cell 5: 729-735
34. Huyer G, Piluek WF, Fansler Z, Kreft SG, Hochstrasser M, Brodsky JL and Michaelis S (2004) Distinct machinery is required in Saccharomyces cerevisiae for the endoplasmic reticulum-associated degradation of a muttispanning membrane protein and a soluble luminal protein. J. Biol. Chem. 279: 38369-8378
35. Plemper RK, Bohmler S, Bordallo J, Sommer T and Wolf DH (1997) Mutant analysis links the translocon and BiP to retrograde protein transport for ER degradation. Nature 388: 891-895
36. Plemper RK, Egner R, Kuchler K and Wolf DH (1998) Endoplasmic reticulum degradation of a mutated ATP-binding cassette transporter Pdr5 proceeds in a concerted action of Sec61 and the proteasome. J. Biol. Chem. 273: 32848-32856
37. Brodsky JL, Werner ED, Dubas ME, Goeckeler JL, Kruse KB and McCracken AA (1999) The requirement for molecular chaperones during endoplasmic reticulum-associated protein degradation demonstrates that protein export and import are mechanistically distinct. J. Biol. Chem. 274: 3453-3460
38. Gillece P, Luz JM, Lennarz WJ, de La Cruz FJ and Romisch K (1999) Export of a cysteine-free misfolded secretory protein from the endoplasmic reticulum for degradation requires interaction with protein disulfide isomerase. J. Cell Biol. 147: 1443-1456
39. Knop M, Hauser N and Wolf DH (1996) N-glycosylation affects endoplasmic reticulum degradation of a mutated derivative of carboxypeptidase yscY in yeast. Yeast 12: 1229-1238
40. Spear ED and Ng DT (2005) Single, context-specific glycans can target misfolded glycoproteins for ER-associated degradation. J. Cell Biol. 169: 73-82
41. Rapoport TA, Matlack KE, Plath K, Misselwitz B and Staeck O (1999) Posttranslational protein translocation across the membrane of the endoplasmic reticulum. Biol. Chem. 380: 1143-1150
42. Clemons Jr WM, Menetret JF, Akey CW and Rapoport TA (2004) Structural insight into the protein translocation channel. Curr. Opin. Struct. Biol. 14: 390-396
43. Pilon M, Schekman R and Romisch K (1997) Sec61p mediates export of a misfolded secretory protein from the endoplasmic reticulum to the cytosol for degradation. EMBO J. 16: 4540-1548
44. Zhou M and Schekman R (1999) The engagement of Sec61p in the ER dislocation process. Mol. Cell 4: 925-934
45. Richly H, Rape M, Braun S, Rumpf S, Hoege C and Jentsch S (2005) A series of ubiquitin binding factors connects CDC48/p97 to substrate multiubiquitylation and proteasomal targeting. Cell 120: 73-84
46. Jarosch E, Taxis C, Volkwein C, Bordallo J, Finley D, Wolf DH and Sommer T (2002) Protein dislocation from the ER requires polyubiquitination and the AAA-ATPase Cdc48. Nat. Cell Biol. 4: 134-139
47. Braun S, Matuschewski K, Rape M, Thorns S and Jentsch S (2002) Role of the ubiquitin-selective CDC48(UFD1/NPL4)chaperone (segregase) in ERAD of OLE1 and other substrates. EMBO J. 21: 615-621
48. Hitchcock AL, Krebber H, Frietze S, Lin A, Latterich M and Silver PA (2001) The conserved npl4 protein complex mediates proteasome-dependent membrane-bound transcription factor activation. Mol. Biol. Cell 12: 3226-3241
49. Rape M, Hoppe T, Gorr I, Kalocay M, Richly H and Jentsch S (2001) Mobilization of processed, membrane-tethered SPT23 transcription factor by CDC48(UFD1/NPL4), a ubiquitin-selective chaperone. Cell 107: 667-677
50. Biederer T, Volkwein C and Sommer T (1997) Role of Cue1p in ubiquitination and degradation at the ER surface. Science 278: 1806-1809
51. Sommer T and Jentsch S (1993) A protein translocation defect linked to ubiquitin conjugation at the endoplasmic reticulum. Nature 365: 176-179
52. Friedlander R, Jarosch E, Urban J, Volkwein C and Sommer T (2000) A regulatory link between ER-associated protein degradation and the unfolded-protein response. Nat. Cell Biol. 2: 379-384
53. Hampton RY, Gardner RG and Rine J (1996) Role of 26S proteasome and HRD genes in the degradation of 3-hydroxy-3- methylglutaryl-CoA reductase, an integral endoplasmic reticulum membrane protein. Mol. Biol. Cell 7: 2029-2044
54. Knop M, Finger A, Braun T, Hellmuth K and Wolf DH (1996) Der1, a novel protein specifically required for endoplasmic reticulum degradation in yeast. EMBO J. 15: 753-763
55. Bordallo J, Plemper RK, Finger A and Wolf DH (1998) Der3p/Hrd1p is required for endoplasmic reticulum-associated degradation of misfolded lumenal and integral membrane proteins. Mol. Biol. Cell 9: 209-222
56. Plemper RK, Bordallo J, Deak PM, Taxis C, Hitt R and Wolf DH (1999) Genetic interactions of Hrd3p and Der3p/Hrd1p with Sec61p suggest a retrotranslocation complex mediating protein transport for ER degradation. J. Cell Sci. 112: 4123-4134
57. Haynes CM, Titus EA and Cooper AA (2004) Degradation of misfolded proteins prevents ER-derived oxidative stress and cell death. Mol. Cell 15: 767-776
58. Patil CK, Li H and Walter P (2004) Gcn4p and novel upstream activating sequences regulate targets of the unfolded protein response. PLoS Biol. 2: E246
59. Hinnebusch AG (1997) Translational regulation of yeast GCN4. A window on factors that control initiator-TRNA binding to the ribosome. J. Biol. Chem. 272: 21661-21664
60. Tirasophon W, Welihinda AA and Kaufman RJ (1998) 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
61. Bertolotti A, Wang X, Novoa I, Jungreis R, Schlessinger K, Cho JH, West AB and Ron D (2001) Increased sensitivity to dextran sodium sulfate colitis in IRE1beta- deficient mice. J. Clin. Invest. 107: 585-593
62. Calfon M, Zeng H, Urano F, Till JH, Hubbard SR, Harding HP, Clark S and Ron D (2002) IRE1 couples endoplasmic reticulum load to secretory capacity by processing the XBP-1 mRNA. Nature 415: 92-96
63. Yoshida H, Matsui T, Yamamoto A, Okada T and Mori K (2001) 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
64. Clauss IM, Gravallese EM, Darling JM, Shapiro F, Glimcher MJ and Glimcher LH (1993) In situ hybridization studies suggest a role for the basic region-leucine zipper protein hXBP-1 in exocrine gland and skeletal development during mouse embryogenesis. Dev. Dyn. 197: 146-156
65. Lee AH, Iwakoshi NN and Glimcher LH (2003) XBP-1 regulates a subset of endoplasmic reticulum resident chaperone genes in the unfolded protein response. Mol. Cell. Biol. 23: 7448-7459
66. Yoshida H, Haze K, Yanagi H, Yura T and Mori K (1998) Identification of the cis-acting endoplasmic reticulum stress response element responsible for transcriptional induction of mammalian glucose- regulated proteins. Involvement of basic leucine zipper transcription factors. J. Biol. Chem. 273: 33741-33749
67. Haze K, Yoshida H, Yanagi H, Yura T and Mori K (1999) Mammalian transcription factor ATF6 is synthesized as a transmembrane protein and activated by proteolysis in response to endoplasmic reticulum stress. Mol. Biol. Cell 10: 3787-3799
68. Yoshida H, Okada T, Haze K, Yanagi H, Yura T, Negishi M and Mori K (2000) ATF6 activated by proteolysis binds in the presence of NF-Y (CBF) directly to the cis-acting element responsible for the mammalian unfolded protein response. Mol. Cell. Biol. 20: 6755-6767
69. Wang Y, Shen J, Arenzana N, Tirasophon W, Kaufman RJ and Prywes R (2000) Activation of ATF6 and an ATF6 DNA binding site by the endoplasmic reticulum stress response. J. Biol. Chem. 275: 27013-27020
70. Shen J, Chen X, Hendershot L and Prywes R (2002) ER stress regulation of ATF6 localization by dissociation of BiP/GRP78 binding and unmasking of Golgi localization signals. Dev. Cell 3: 99-111
71. Ye J, Rawson RB, Komuro R, Chen X, Dave UP, Prywes R, Brown MS and Goldstein JL (2000) ER stress induces cleavage of membrane-bound ATF6 by the same proteases that process SREBPs. Mol. Cell 6: 1355-1364
72. Yoshida H, Matsui T, Hosokawa N, Kaufman RJ, Nagata K and Mori K (2003) A time-dependent phase shift in the mammalian unfolded protein response. Dev. Cell 4: 265-271
73. Tokunaga F, Brostrom C, Koide T and Arvan P (2000) Endoplasmic reticulum (ER)-associated degradation of misfolded N-linked glycoproteins is suppressed upon inhibition of ER mannosidase I. J. Biol. Chem. 275: 40757-40764
74. Tsai B, Rodighiero C, Lencer WI and Rapoport TA (2001) Protein disulfide isomerase acts as a redox-dependent chaperone to unfold cholera toxin. Cell 104: 937-948
75. Knittler MR, Dirks S and Haas IG (1995) Molecular chaperones involved in protein degradation in the endoplasmic reticulum: Quantitative interaction of the heat shock cognate protein BiP with partially folded immunoglobulin light chains that are degraded in the endoplasmic reticulum. Proc. Natl. Acad. Sci. USA 92: 1764-1768
76. Wiertz EJ, Tortorella D, Bogyo M, Yu J, Mothes W, Jones TR, Rapoport TA and Ploegh HL (1996) Sec61-mediated transfer of a membrane protein from the endoplasmic reticulum to the proteasome for destruction. Nature 384: 432-438
77. Bebok Z, Mazzochi C, King SA, Hong JS and Sorscher EJ (1998) The mechanism underlying cystic fibrosis transmembrane conductance regulator transport from the endoplasmic reticulum to the proteasome includes Sec61beta and a cytosolic, deglycosylated intermediary. J. Biol. Chem. 273: 29873-29878
78. Ye Y, Meyer HH and Rapoport TA (2001) The AAA ATPase Cdc48/p97 and its partners transport proteins from the ER into the cytosol. Nature 414: 652-656
79. Bays NW, Wilhovsky SK, Goradia A, Hodgkiss-Harlow K and Hampton RY (2001) HRD4/NPL4 is required for the proteasomal processing of ubiquitinated ER proteins. Mol. Biol. Cell 12: 4114-4128
80. Meyer HH, Shorter JG, Seemann J, Pappin D and Warren G (2000) A complex of mammalian ufd1 and npl4 links the AAA-ATPase, p97, to ubiquitin and nuclear transport pathways. EMBO J. 19: 2181-2192
81. Lilley BN and Ploegh HL (2004) A membrane protein required for dislocation of misfolded proteins from the ER. Nature 429: 834-840
82. Ye Y, Shibata Y, Yun C, Ron D and Rapoport TA (2004) A membrane protein complex mediates retro-translocation from the ER lumen into the cytosol. Nature 429: 841-847
83. Connell P, Ballinger CA, Jiang J, Wu Y, Thompson LJ, Hohfeld J and Patterson C (2001) The co-chaperone CHIP regulates protein triage decisions mediated by heat-shock proteins. Nat. Cell Biol. 3: 93-96
84. Jiang J, Ballinger CA, Wu Y, Dai Q, Cyr DM, Hohfeld J and Patterson C (2001) CHIP is a U-box-dependent E3 ubiquitin ligase: Identification of Hsc70 as a target for ubiquitylation. J. Biol. Chem. 276: 42938-42944
85. Meacham GC, Patterson C, Zhang W, Younger JM and Cyr DM (2001) The Hsc70 co-chaperone CHIP targets immature CFTR for proteasomal degradation. Nat. Cell Biol. 3: 100-105
86. Murata S, Minami Y, Minami M, Chiba T and Tanaka K (2001) CHIP is a chaperone-dependent E3 ligase that ubiquitylates unfolded protein. EMBO Rep. 2: 1133-1138
87. Shimura H, Schlossmacher MG, Hattori N, Frosch MP, Trockenbacher A, Schneider R, Mizuno Y, Kosik KS and Selkoe DJ (2001) Ubiquitination of a new form of alpha-synuclein by parkin from human brain: Implications for Parkinson's disease. Science 293: 263-269
88. Chung KK, Zhang Y, Lim KL, Tanaka Y, Huang H, Gao J, Ross CA, Dawson VL and Dawson TM (2001) Parkin ubiquitinates the alpha-synuclein-interacting protein, synphilin-1: Implications for Lewy-body formation in Parkinson disease. Nat. Med. 7: 1144-1150
89. Imai Y, Soda M, Inoue H, Hattori N, Mizuno Y and Takahashi R (2001) An unfolded putative transmembrane polypeptide, which can lead to endoplasmic reticulum stress, is a substrate of Parkin. Cell 105: 891-902
90. Hinnebusch A (2000) Mechanism and regulation of initiator methionyl-tRNA binding to ribosomes. In Translational Control of Gene Expression, Sonenberg N, Hershey JWB, Mathews MB, eds (Cold Spring Harbor: Cold Spring Harbor Laboratory Press) pp. 185-244
91. Clemens MJ (2001) Initiation factor elF2 alpha phosphorylation in stress responses and apoptosis. Prog. Mol. Subcell Biol. 27: 57-89
92. Proud CG (2005) elF2 and the control of cell physiology. Semin. Cell Dev. Biol. 16: 3-12
93. Harding HP, Novoa I, Zhang Y, Zeng H, Wek R, Schapira M and Ron D (2000) Regulated translation initiation controls stress-induced gene expression in mammalian cells. Mol. Cell 6: 1099-1108
94. Sood R, Porter AC, Olsen DA, Cavener DR and Wek RC (2000) A mammalian homologue of GCN2 protein kinase important for translational control by phosphorylation of eukaryotic initiation factor-2alpha. Genetics 154: 787-801
95. Kaufman RJ (2000) Double-stranded RNA-activated protein kinase, PKR. In Translational Control of Gene Expression, Sonenberg N, Hershey JWB, Mathews MB, eds (Cold Spring Harbor: Cold Spring Harbor Laboratory Press) pp. 503-528
96. Williams BR (1999) PKR; a sentinel kinase for cellular stress. Oncogene 18: 6112-6120
97. Chen JJ (2000) Heme-regulated elF2α kinase. In Translational Control of Gene Expression, Sonenberg N, Hershey JWB, Mathews MB, eds (Cold Spring Harbor: Cold Spring Harbor Laboratory Press) pp. 529-546
98. Ron D and Harding HP (2000) PERK and translational control by stress in the endoplasmic reticulum. In Translational Control of Gene Expression Sonenberg N, Hershey JWB, Mathews MB, eds (Cold Spring Harbor: Cold Spring Harbor Laboratory Press) pp. 547-560
99. Harding HP, Zhang Y and Ron D (1999) Protein translation and folding are coupled by an endoplasmic-retculum- resident kinase. Nature 397: 271-274
100. Liu CY, Schroder M and Kaufman RJ (2000) Ligand-independent dimerization activates the stress response kinases IRE1 and PERK in the lumen of the endoplasmic reticulum. J. Biol. Chem. 275: 24881-24885
101. Okamura K, Kimata Y, Higashio H, Tsuru A and Kohno K (2000) Dissociation of Kar2p/BiP from an ER sensory molecule, Ire1p, triggers the unfolded protein response in yeast. Biochem. Biophys. Res. Commun. 279: 445-450
102. Harding HP, Zhang Y, Bertolotti A, Zeng H and Ron D (2000) Perk is essential for translational regulation and cell survival during the unfolded protein response. Mol. Cell 5: 897-904
103. Fawcett TW, Martindale JL, Guyton KZ, Hai T and Holbrook NJ (1999) Complexes containing activating transcription factor (ATF)/ cAMP-responsive-element-binding protein (CREB) interact with the CCAAT/ enhancer-binding protein (C/EBP)-ATF composite site to regulate Gadd153 expression during the stress response. Biochem. J. 339: 135-141
104. Fernandez J, Yaman I, Sarnow P, Snider MD and Hatzoglou M (2002) Regulation of internal ribosomal entry site-mediated translation by phosphorylation of the translation initiation factor elF2alpha. J. Biol. Chem. 277: 19198-19205
105. Fernandez J, Yaman I, Merrick WC, Koromilas A, Wek RC, Sood R, Hensold J and Hatzoglou M (2002) Regulation of internal ribosome entry site-mediated translation by eukaryotic initiation factor-2alpha phosphorylation and translation of a small upstream open reading frame. J. Biol. Chem. 277: 2050-2058
106. Tanaka T, Tsujimura T, Takeda K, Sugihara A, Maekawa A and Terada N et al. (1998) Targeted disruption of ATF4 discloses its essential role in the formation of eye lens fibres. Genes Cells 3: 801-810
107. Scheuner D, Song B, McEwen E, Liu C, Laybutt R, Gillespie P, Saunders T, Bonner-Weir S and Kaufman RJ (2001) Translational control is required for the unfolded protein response and in vivo glucose homeostasis. Mol. Cell 7: 1165-1176
108. Harding HP, Zhang Y, Zeng H, Novoa I, Lu PD, Calfon M, Sadri N, Yun C, Popko B, Paules R, Stojdl DF, Bell JC, Hettmann T, Leiden JM and Ron D (2003) An integrated stress response regulates amino acid metabolism and resistance to oxidative stress. Mol. Cell 11: 619-633
109. Ma Y, Brewer JW, Diehl JA and Hendershot LM (2002) Two distinct stress signaling pathways converge upon the CHOP promoter during the mammalian unfolded protein response. J. Mol. Biol. 318: 1351-1365
110. Luo S, Baumeister P, Yang S, Abcouwer SF and Lee AS (2003) Induction of Grp78/BiP by translational block: Activation of the Grp78 promoter by ATF4 through and upstream ATF/CRE site independent of the endoplasmic reticulum stress elements. J. Biol. Chem. 278: 37375-37385
111. Wang XZ, Lawson B, Brewer JW, Zinszner H, Senjay A, Mi LJ, Boorstein R, Kreibich G, Hendershot LM and Ron D (1996) Signals from the stressed endoplasmic reticulum induce C/EBP-homologous protein (CHOP/GADD153). Mol. Cell. Biol. 16: 4273-4280
112. Zinszner H, Kuroda M, Wang X, Batchvarova N, Lightfoot FIT and Remotti H et al. (1998) CHOP is implicated in programmed cell death in response to impaired function of the endoplasmic reticulum. Genes Dev. 12: 982-995
113. Jousse C, Bruhat A, Carraro V, Urano F, Ferrara M, Ron D and Fafournoux P (2001) Inhibition of CHOP translation by a peptide encoded by an open reading frame localized in the chop 5′UTR. Nucleic Acids Res. 29: 4341-4351
114. Ubeda M, Wang XZ, Zinszner H, Wu I, Habener JF and Ron D (1996) Stress-induced binding of the transcriptional factor CHOP to a novel DNA control element. Mol. Cell. Biol. 16: 1479-1489
115. Ubeda M, Vallejo M and Habener JF (1999) CHOP enhancement of gene transcription by interactions with Jun/Fos AP- 1 complex proteins. Mol. Cell. Biol. 19: 7589-7599
116. Marciniak SJ, Yun CY, Oyadomari S, Novoa I, Zhang Y, Jungreis R, Nagata K, Harding HP and Ron D (2004) CHOP induces death by promoting protein synthesis and oxidation in the stressed endoplasmic reticulum. Genes Dev. 18: 3066-3077
117. Brush MH, Weiser DC and Shenolikar S (2003) Growth arrest and DNA damage-inducible protein GADD34 targets protein phosphatase 1 alpha to the endoplasmic reticulum and promotes dephosphorylation of the alpha subunit of eukaryotic translation initiation factor 2. Mol. Cell. Biol. 23: 1292-1303
118. Novoa I, Zeng H, Harding HP and Ron D (2001) Feedback inhibition of the unfolded protein response by GADD34-mediated dephosphorylation of elF2alpha. J. Cell Biol. 153: 1011-1022
119. Aggen JB, Nairn AC and Chamberlin R (2000) Regulation of protein phosphatase-1. Chem. Biol. 7: R13-R23
120. Jiang HY, Wek SA, McGrath BC, Lu D, Hai T, Harding HP, Wang X, Ron D, Cavener DR and Wek RC (2004) Activating transcription factor 3 is integral to the eukaryotic initiation factor 2 kinase stress response. Mol. Cell. Biol. 24: 1365-1377
121. Novoa I, Zhang Y, Zeng H, Jungreis R, Harding HP and Ron D (2003) Stress-induced gene expression requires programmed recovery from translational repression. EMBO J. 22: 1180-1187
122. Kojima E, Takeuchi A, Haneda M, Yagi A, Hasegawa T, Yamaki K, Takeda K, Akira S, Shimokata K and Isobe K (2003) The function of GADD34 is a recovery from a shutoff of protein synthesis induced by ER stress: elucidation by GADD34-deficient mice. FASEB J. 17: 1573-1575
123. Jousse C, Oyadomari S, Novoa I, Lu P, Zhang Y, Harding HP and Ron D (2003) Inhibition of a constitutive translation initiation factor 2alpha phosphatase, CReP, promotes survival of stressed cells. J. Cell Biol. 163: 767-775
124. Kebache S, Cardin E, Nguyen DT, Chevet E and Larose L (2004) Nck-1 antagonizes the endoplasmic reticulum stress-induced inhibition of translation. J. Biol. Chem. 279: 9662-9671
125. Cullinan SB, Zhang D, Hannink M, Arvisais E, Kaufman RJ and Diehl JA (2003) Nrf2 is a direct PERK substrate and effector of PERK-dependent cell survival. Mol. Cell. Biol. 23: 7198-7209
126. Venugopal R and Jaiswal AK (1998) Nrf2 and Nrf1 in association with Jun proteins regulate antioxidant response element-mediated expression and coordinated induction of genes encoding detoxifying enzymes. Oncogene 17: 3145-3156
127. Venugopal R and Jaiswal AK (1996) Nrf1 and Nrf2 positively and c-Fos and Fra1 negatively regulate the human antioxidant response element-mediated expression of NAD(P)H:qUinone oxidoreductase1 gene. Proc. Natl. Acad. Sci. USA 93: 14960-14965
128. Itoh K, Chiba T, Takahashi S, Ishii T, Igarashi K, Katoh Y, Oyake T, Hayashi N, Satoh K, Hatayama I, Yamamoto M and Nabeshima Y (1997) An Nrf2/small Maf heterodimer mediates the induction of phase II detoxifying enzyme genes through antioxidant response elements. Biochem. Biophys. Res. Commun. 236: 313-322
129. Urano F, Bertolotti A and Ron D (2000) IRE1 and efferent signaling from the endoplasmic reticulum. J. Cell Sci. 113 (Part 21): 3697-3702
130. Urano F, Wang X, Bertolotti A, Zhang Y, Chung P, Harding HP and Ron D (2000) Coupling of stress in the ER to activation of JNK protein kinases by transmembrane protein kinase IRE1. Science 287: 664-666
131. Nishitoh H, Saitoh M, Mochida Y, Takeda K, Nakano H, Rothe M, Miyazono K and Ichijo H (1998) ASK1 is essential for JNK/SAPK activation by TRAF2. Mol. Cell 2: 389-395
132. Nishitoh H, Matsuzawa A, Tobiume K, Saegusa K, Takeda K and Inoue K et al. (2002) ASK1 is essential for endoplasmic reticulum stress-induced neuronal cell death triggered by expanded polyglutamine repeats. Genes Dev. 16: 1345-1355
133. Nakanishi K, Sudo T and Morishima N (2005) Endoplasmic reticulum stress signaling transmitted by ATF6 mediates apoptosis during muscle development. J. Cell Biol. 169: 555-560
134. Matsumoto M, Minami M, Takeda K, Sakao Y and Akira S (1996) Ectopic expression of CHOP (GADD153) induces apoptosis in M1 myeloblastic leukemia cells. FEBS Lett. 395: 143-147
135. McCullough KD, Martindale JL, Klotz LO, Aw TY and Holbrook NJ (2001) Gadd153 sensitizes cells to endoplasmic reticulum stress by down-regulating Bcl2 and perturbing the cellular redox state. Mol. Cell. Biol. 21: 1249-1259
136. Yamaguchi H and Wang HG (2004) CHOP is involved in endoplasmic reticulum stress-induced apoptosis by enhancing DR5 expression in human carcinoma cells. J. Biol. Chem. 279: 45495-45502
137. Schneider P and Tschopp J (2000) Apoptosis induced by death receptors. Pharm. Acta. Helv. 74: 281-286
138. Lu PD, Jousse C, Marciniak SJ, Zhang Y, Novoa I, Scheuner D, Kaufman RJ, Ron D and Harding HP (2004) Cytoprotection by pre-emptive conditional phosphorylation of translation initiation factor 2. EMBO J. 23: 169-179
139. Boyce M, Bryant KF, Jousse C, Long K, Harding HP, Scheuner D, Kaufman RJ, Ma D, Coen DM, Ron D and Yuan J (2005) A selective inhibitor of elF2alpha dephosphorylation protects cells from ER stress. Science 307: 935-939
140. Krajewski S, Tanaka S, Takayama S, Schibler MJ, Fenton W and Reed JC (1993) Investigation of the subcellular distribution of the bcl-2 oncoprotein: Residence in the nuclear envelope, endoplasmic reticulum, and outer mitochondrial membranes. Cancer Res. 53: 4701-4714
141. Chen-Levy Z, Nourse J and Cleary ML (1989) The bcl-2 candidate protooncogene product is a 24-kilodalton integral-membrane protein highly expressed in lymphoid cell lines and lymphomas carrying the t(14;18) translocation. Mol. Cell. Biol. 9: 701-710
142. Kuwana T and Newmeyer DD (2003) Bcl-2-family proteins and the role of mitochondria in apoptosis. Curr. Opin. Cell Biol. 15: 691-699
143. Annis MG, Yethon JA, Leber B and Andrews DW (2004) There is more to life and death than mitochondria: Bcl-2 proteins at the endoplasmic reticulum. Biochim. Biophys. Acta 1644: 115-123
144. Thomenius MJ and Distelhorst CW (2003) Bcl-2 on the endoplasmic reticulum: Protecting the mitochondria from a distance. J. Cell Sci.116: 4493-4499
145. Wang NS, Unkila MT, Reineks EZ and Distelhorst CW (2001) Transient expression of wild-type or mitochondrially targeted Bcl-2 induces apoptosis, whereas transient expression of endoplasmic reticulum-targeted Bcl-2 is protective against Bax-induced cell death. J. Biol. Chem. 276: 44117-44128
146. Thomenius MJ, Wang NS, Reineks EZ, Wang Z and Distelhorst CW (2003) Bcl-2 on the endoplasmic reticulum regulates Bax activity by binding to BH3-only proteins. J. Biol. Chem. 278: 6243-6250
147. Modshima N, Nakanishi K, Tsuchiya K, Shibata T and Seiwa E (2004) Translocation of Bim to the endoplasmic reticulum (ER) mediates ER stress signaling for activation of caspase-12 during ER stress-induced apoptosis. J. Biol. Chem. 279: 50375-50381
148. Germain M, Mathai JP, McBride HM and Shore GC (2005) Endoplasmic reticulum BIK initiates DRP1-regulated remodelling of mitochondrial cristae during apoptosis. EMBO J. 24: 1546-1556
149. Germain M, Mathai JP and Shore GC (2002) BH-3-only BIK functions at the endoplasmic reticulum to stimulate cytochrome c release from mitochondria. J. Biol. Chem. 277: 18053-18060
150. Mathai JP, Germain M, Marcellus RC and Shore GC (2002) Induction and endoplasmic reticulum location of BIK/NBK in response to apoptotic signaling by E1A and p53. Oncogene 21: 2534-2544
151. Mathai JP, Germain M and Shore GC (2005) BH3-only Bik regulates BAX,BAK-dependent release of Ca2+ from endoplasmic reticulum stores and mitochondrial apoptosis during stress-induced cell death. J. Biol. Chem. 280: 23829-23836
152. Reimertz C, Kogel D, Rami A, Chittenden T and Prehn JH (2003) Gene expression during ER stress-induced apoptosis in neurons: Induction of the BH3-only protein Bbc3/PUMA and activation of the mitochondrial apoptosis pathway. J. Cell Biol. 162: 587-597
153. Luo X, He Q, Huang Y and Sheikh MS (2005) Transcriptional upregulation of PUMA modulates endoplasmic reticulum calcium pool depletion-induced apoptosis via Bax activation. Cell Death Differ. 12: 1310-1318
154. Zong WX, Lindsten T, Ross AJ, MacGregor GR and Thompson CB (2001) BH3-only proteins that bind pro-survival Bcl-2 family members fail to induce apoptosis in the absence of Bax and Bak. Genes Dev. 15: 1481-1486
155. Wei MC, Zong WX, Cheng EH, Lindsten T, Panoutsakopoulou V and Ross AJ et al. (2001) Proapoptotic BAX and BAK: A requisite gateway to mitochondrial dysfunction and death. Science 292: 727-730
156. 2mobilization promotes cytochrome c release during apoptosis. J. Biol. Chem. 277: 20301-20308
157. Nutt LK, Pataer A, Pahler J, Fang B, Roth J, McConkey DJ and Swisher SG (2002) Bax and Bak promote apoptosis by modulating endoplasmic reticular and mitochondrial Ca2+ stores. J. Biol. Chem. 277: 9219-9225
158. Oakes SA, Scorrano L, Opferman JT, Bassik MC, Nishino M and Pozzan T et al. (2005) Proapoptotic BAX and BAK regulate the type 1 inositol trisphosphate receptor and calcium leak from the endoplasmic reticulum. Proc. Natl. Acad. Sci. USA 102: 105-110
159. 2+: A control point for apoptosis. Science 300: 135-139
160. Zong WX, Li C, Hatzivassiliou G, Lindsten T, Yu QC, Yuan J and Thompson CB (2003) Bax and Bak can localize to the endoplasmic reticulum to initiate apoptosis. J. Cell Biol. 162: 59-69
161. Klee M and Pimentel-Muinos FX (2005) Bcl-X(L) specifically activates Bak to induce swelling and restructuring of the endoplasmic reticulum. J. Cell Biol. 168: 723-734
162. Nakagawa T, Zhu H, Morishima N, Li E, Xu J, Yankner BA and Yuan J (2000) Caspase-12 mediates endoplasmic-reticulum-specific apoptosis and cytotoxicity by amyloid-beta. Nature 403: 98-103
163. Nakagawa T and Yuan J (2000) Cross-talk between two cysteine protease families. Activation of caspase-12 by calpain in apoptosis. J. Cell Biol. 150: 887-894
164. Yoneda T, Imaizumi K, Oono K, Yui D, Gomi F, Katayama T and Tohyama M (2001) Activation of caspase-12, an endoplastic reticulum (ER) resident caspase, through tumor necrosis factor receptor-associated factor 2 dependent mechanism in response to the ER stress. J. Biol. Chem. 276: 13935-13940
165. Rao RV, Poksay KS, Castro-Obregon S, Schilling B, Row RH, del Rio G,
166. Rao RV, Castro-Obregon S, Frankowski H, Schuler M, Stoka V, del Rio G, Bredesen DE and Ellerby HM (2002) Coupling endoplasmic reticulum stress to the cell death program. An Apaf-1-independent intrinsic pathway. J. Biol. Chem. 277: 21836-21842
167. Modshima N, Nakanishi K, Takenouchi H, Shibata T and Yasuhiko Y (2002) An endoplasmic reticulum stress-specific caspase cascade in apoptosis. Cytochrome c-independent activation of caspase-9 by caspase-12. J. Biol. Chem. 277: 34287-34294
168. Chandler JM, Cohen GM and MacFarlane M (1998) Different subcellular distribution of caspase-3 and caspase-7 following Fas-induced apoptosis in mouse liver. J. Biol. Chem. 273: 10815-10818
169. Rao RV, Hermel E, Castro-Obregon S, del Rio G, Ellerby LM, Ellerby HM and Bredesen DE (2001) Coupling endoplasmic reticulum stress to the cell death program. Mechanism of caspase activation. J. Biol. Chem. 276: 33869-33874
170. Song L, De Sarno P and Jope RS (2002) Central role of glycogen synthase kinase-3b inendoplasmic reticulum stress-induced caspase-3 activation. J. Biol. Chem. 12: 12
171. Saleh M, Vaillancourt JP, Graham RK, Huyck M, Srinivasula SM, Alnemri ES, Steinberg MH, Nolan V, Baldwin CT, Hotchkiss RS, Buchman TG, Zehnbauer BA, Hayden MR, Farrer LA, Roy S and Nicholson DW (2004) Differential modulation of endotoxin responsiveness by human caspase-12 polymorphisms. Nature 429: 75-79
172. Fischer H, Koenig U, Eckhart L and Tschachler E (2002) Human caspase 12 has acquired deleterious mutations. Biochem. Biophys. Res. Commun. 293: 722-726
173. Hitomi J, Katayama T, Eguchi Y, Kudo T, Taniguchi M, Koyama Y, Manabe T, Yamagishi S, Bando Y, Imaizumi K, Tsujimoto Y and Tohyama M (2004) Involvement of caspase-4 in endoplasmic reticulum st. J. Cell Biol. 165: 347-356