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Role of the unfolded protein response in cell death

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Abstract

Unfolded protein response (UPR) is an important genomic response to endoplasmic reticulum (ER) stress. The ER chaperones, GRP78 and Gadd153, play critical roles in cell survival or cell death as part of the UPR, which is regulated by three signaling pathways: PERK/ATF4, IRE1/XBP1 and ATF6. During the UPR, accumulated unfolded protein is either correctly refolded, or unsuccessfully refolded and degraded by the ubiquitin-proteasome pathway. When the unfolded protein exceeds a threshold, damaged cells are committed to cell death, which is mediated by ATF4 and ATF6, as well as activation of the JNK/AP-1/Gadd153-signaling pathway. Gadd153 suppresses activation of Bcl-2 and NF-κB. UPR-mediated cell survival or cell death is regulated by the balance of GRP78 and Gadd153 expression, which is coregulated by NF-κB in accordance with the magnitude of ER stress. Less susceptibility to cell death upon activation of the UPR may contribute to tumor progression and drug resistance of solid tumors.

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Abbreviations

UPR:

unfolded protein response

ER:

endoplasmic reticulum

GRP:

glucose-regulated protein

BiP:

immunoglobulin binding protein

Gadd153:

growth arrest and DNA damage-inducible protein 153

PERK:

double-stranded RNA-activated protein kinase-like ER kinase

ATF:

activating transcription factor

IRE-1:

high inositol-requiring 1

XBP1:

X-box binding protein 1

JNK:

c-Jun N-terminal kinase

ASK1:

apoptosis signal-regulating kinase

CHOP/Gadd153:

CCAAT/enhancer-binding protein (C/EBP)-homologous protein/growth arrest and DNA damage-inducible protein 153

eIF:

eukaryotic initiation factor

ERAD:

ER-associated degradation

EDEM:

ER degradation-enhancing α-mannosidase-like protein

TRF2:

TNF receptor-associated factor 2

bZIP:

basic leucine zipper

References

  1. Schmitz A, Herzog V. Endoplasmic reticulum-associated degradation: Exceptions to the rule. Eur J Cell Biol 2004; 83: 501–509.

    Article  PubMed  Google Scholar 

  2. Rutkowski DT, Kaufman RJ. A trip to the ER: Coping with stress. Trends Cell Biol 2004; 14: 20–28.

    Article  CAS  PubMed  Google Scholar 

  3. Rao RV, Peel A, Logvinova A, et al. Coupling endoplasmic reticulum stress to the cell death program: Role of the ER chaperone GRP78. FEBS Lett 2002; 514: 122–128.

    CAS  PubMed  Google Scholar 

  4. Schroder M, Kaufman RJ. ER stress and the unfolded protein response. Mutat Res 2005; 569: 29–63.

    PubMed  Google Scholar 

  5. Szczesna-Skorupa E, Chen CD, Liu H, Kemper B. Gene expression changes associated with the endoplasmic reticulum stress response induced by microsomal cytochrome p450 overproduction. J Biol Chem 2004; 279: 13953–13961.

    Article  CAS  PubMed  Google Scholar 

  6. Koumenis C, Naczki C, Koritzinsky M, et al. Regulation of protein synthesis by hypoxia via activation of the endoplasmic reticulum kinase PERK and phosphorylation of the translation initiation factor eIF2alpha. Mol Cell Biol 2002; 22: 7405–7416.

    Article  CAS  PubMed  Google Scholar 

  7. Ahner A, Brodsky JL. Checkpoints in ER-associated degradation: Excuse me, which way to the proteasome? Trends Cell Biol 2004; 14: 474–478.

    Article  CAS  PubMed  Google Scholar 

  8. Sargsyan E, Baryshev M, Mkrtchian S. The physiological unfolded protein response in the thyroid epithelial cells. Biochem Biophys Res Commun 2004; 322: 570–576.

    Article  CAS  PubMed  Google Scholar 

  9. Yamaguchi H, Wang HG. CHOP is involved in endoplasmic reticulum stress-induced apoptosis by enhancing DR5 expression in human carcinoma cells. J Biol Chem 2004; 279: 45495–45502.

    CAS  PubMed  Google Scholar 

  10. Rao RV, Castro-Obregon S, Frankowski H, et al. Coupling endoplasmic reticulum stress to the cell death program. An Apaf-1-independent intrinsic pathway. J Biol Chem 2002; 277: 21836–21842.

    CAS  PubMed  Google Scholar 

  11. Yoneda T, Imaizumi K, Oono K, et al. 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 2001; 276: 13935–13940.

    CAS  PubMed  Google Scholar 

  12. Bowser DN, Petrou S, Panchal RG, Smart ML, Williams DA. Release of mitochondrial Ca2+ via the permeability transition activates endoplasmic reticulum Ca2+ uptake. FASEB J 2002; 16: 1105–1107.

    CAS  PubMed  Google Scholar 

  13. Scorrano L, Oakes SA, Opferman JT, et al. BAX and BAK regulation of endoplasmic reticulum Ca2+: A control point for apoptosis. Science 2003; 300: 135–139.

    Article  CAS  PubMed  Google Scholar 

  14. Liu X, Kim CN, Yang J, et al. Induction of apoptotic program in Cell-free extracts: Requirement for dATP and cytochrome c. Cell 1996; 86: 147–157.

    CAS  PubMed  Google Scholar 

  15. Du C, Fang M, Li Y, et al. Smac, a mitochondrial protein that promotes cytochrome c-dependent caspase activation by eliminating IAP inhibition. Cell 2000; 102: 33–42.

    Article  CAS  PubMed  Google Scholar 

  16. Susin SA, Lorenzo HK, Zamzami N, et al. Molecular characterization of mitochondrial apoptosis-inducing factor. Nature 1999; 397: 441–446.

    CAS  PubMed  Google Scholar 

  17. Tsujimoto Y. Cell death regulation by the Bcl-2 protein family in the mitochondria. J Cell Physiol 2003; 195: 158–167.

    Article  CAS  PubMed  Google Scholar 

  18. Zhang K, Kaufman RJ. Signaling the unfolded protein response from the endoplasmic reticulum. J Biol Chem 2004; 279: 25935–25938.

    CAS  PubMed  Google Scholar 

  19. Bertolotti A, Zhang Y, Hendershot LM, Harding HP, Ron D. Dynamic interaction of BiP and ER stress transducers in the unfolded-protein response. Nat Cell Biol 2000; 2: 326–332.

    CAS  PubMed  Google Scholar 

  20. Liu CY, Wong HN, Schauerte JA, Kaufman RJ. The protein kinase/endoribonuclease IRE1alpha that signals the unfolded protein response has a luminal N-terminal ligand-independent dimerization domain. J Biol Chem 2002; 277: 18346–18356.

    CAS  PubMed  Google Scholar 

  21. Blais JD, Filipenko V, Bi M, et al. Activating transcription factor 4 is translationally regulated by hypoxic stress. Mol Cell Biol 2004; 24: 7469–7482.

    Article  CAS  PubMed  Google Scholar 

  22. Proud CG. eIF2 and the control of cell physiology. Semin Cell Dev Biol 2005; 16: 3–12.

    CAS  PubMed  Google Scholar 

  23. Novoa I, Zeng H, Harding HP, Ron D. Feedback inhibition of the unfolded protein response by GADD34-mediated dephosphorylation of eIF2alpha. J Cell Biol 2001; 153: 1011–1022.

    Article  CAS  PubMed  Google Scholar 

  24. Tirasophon W, Lee K, Callaghan B, Welihinda A, Kaufman RJ. The endoribonuclease activity of mammalian IRE1 autoregulates its mRNA and is required for the unfolded protein response. Genes Dev 2000; 14: 2725–2736.

    Article  CAS  PubMed  Google Scholar 

  25. Bertolotti A, Wang X, Novoa I, et al. Increased sensitivity to dextran sodium sulfate colitis in IRE1beta-deficient mice. J Clin Invest 2001; 107: 585–593.

    CAS  PubMed  Google Scholar 

  26. Shuda M, Kondoh N, Imazeki N, 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 2003; 38: 605–614.

    Article  CAS  PubMed  Google Scholar 

  27. Yamamoto K, Yoshida H, Kokame K, Kaufman RJ, Mori K. Differential contributions of ATF6 and XBP1 to the activation of endoplasmic reticulum stress-responsive cis-acting elements ERSE, UPRE and ERSE–II. J Biochem (Tokyo) 2004; 136: 343–350.

    CAS  Google Scholar 

  28. Hong M, Li M, Mao C, Lee AS. Endoplasmic reticulum stress triggers an acute proteasome-dependent degradation of ATF6. J Cell Biochem 2004; 92: 723–732.

    Article  CAS  PubMed  Google Scholar 

  29. Lee AH, Iwakoshi NN, Glimcher LH. XBP-1 regulates a subset of endoplasmic reticulum resident chaperone genes in the unfolded protein response. Mol Cell Biol 2003; 23: 7448–7459.

    CAS  PubMed  Google Scholar 

  30. Lee K, Tirasophon W, Shen X, et al. IRE1-mediated unconventional mRNA splicing and S2P-mediated ATF6 cleavage merge to regulate XBP1 in signaling the unfolded protein response. Genes Dev 2002; 16: 452–466.

    CAS  PubMed  Google Scholar 

  31. Wang Y, Shen J, Arenzana N, Tirasophon W, Kaufman RJ, Prywes R. Activation of ATF6 and an ATF6 DNA binding site by the endoplasmic reticulum stress response. J Biol Chem 2000; 275: 27013–27020.

    CAS  PubMed  Google Scholar 

  32. Yoshida H, Matsui T, Hosokawa N, Kaufman RJ, Nagata K, Mori K. A time-dependent phase shift in the mammalian unfolded protein response. Dev Cell 2003; 4: 265–271.

    Article  CAS  PubMed  Google Scholar 

  33. Hosokawa N, Wada I, Hasegawa K, et al. A novel ER alpha-mannosidase-like protein accelerates ER-associated degradation. EMBO Rep 2001; 2: 415–422.

    CAS  PubMed  Google Scholar 

  34. Gu F, Nguyen DT, Stuible M, Dube N, Tremblay ML, Chevet E. Protein-tyrosine phosphatase 1B potentiates IRE1 signaling during endoplasmic reticulum stress. J Biol Chem 2004; 279: 49689–49693.

    CAS  PubMed  Google Scholar 

  35. Rao RV, Hermel E, Castro-Obregon S, et al. Coupling endoplasmic reticulum stress to the cell death program. Mechanism of caspase activation. J Biol Chem 2001; 276: 33869–33874.

    CAS  PubMed  Google Scholar 

  36. Kaneko M, Niinuma Y, Nomura Y. Activation signal of nuclear factor-kappa B in response to endoplasmic reticulum stress is transduced via IRE1 and tumor necrosis factor receptor-associated factor 2. Biol Pharm Bull 2003; 26: 931–935.

    CAS  PubMed  Google Scholar 

  37. Szegezdi E, Fitzgerald U, Samali A. Caspase-12 and ER-stress-mediated apoptosis: The story so far. Ann N Y Acad Sci 2003; 1010: 186–194.

    Article  CAS  PubMed  Google Scholar 

  38. Nakagawa T, Zhu H, Morishima N, et al. Caspase-12 mediates endoplasmic-reticulum-specific apoptosis and cytotoxicity by amyloid-beta. Nature 2000; 403: 98–103.

    CAS  PubMed  Google Scholar 

  39. Nakagawa T, Yuan J. Cross-talk between two cysteine protease families. Activation of caspase-12 by calpain in apoptosis. J Cell Biol 2000; 150: 887–894.

    Article  CAS  PubMed  Google Scholar 

  40. Wang XZ, Harding HP, Zhang Y, Jolicoeu EM, Kuroda M, Ron D. Cloning of mammalian Ire1 reveals diversity in the ER stress responses. EMBO J 1998; 17: 5708–57017.

    CAS  PubMed  Google Scholar 

  41. Baud V, Karin M. Signal transduction by tumor necrosis factor and its relatives. Trends Cell Biol 2001; 11: 372–377.

    Article  CAS  PubMed  Google Scholar 

  42. Zong WX, Li C, Hatzivassiliou G, et al. Bax and Bak can localize to the endoplasmic reticulum to initiate apoptosis. J Cell Biol 2003; 162: 59–69.

    Article  CAS  PubMed  Google Scholar 

  43. Jayanthi S, Deng X, Noailles PA, Ladenheim B, Cadet JL. Methamphetamine induces neuronal apoptosis via cross-talks between endoplasmic reticulum and mitochondria-dependent death cascades. FASEB J 2004; 18: 238–251.

    Article  CAS  PubMed  Google Scholar 

  44. Urano F, Wang X, Bertolotti A, et al. Coupling of stress in the ER to activation of JNK protein kinases by transmembrane protein kinase IRE1. Science 2000; 287: 664–666.

    Article  CAS  PubMed  Google Scholar 

  45. Nishitoh H, Matsuzawa A, Tobiume K, et al. ASK1 is essential for endoplasmic reticulum stress-induced neuronal cell death triggered by expanded polyglutamine repeats. Genes Dev 2002; 16: 1345–1355.

    Article  CAS  PubMed  Google Scholar 

  46. Kadowaki H, Nishitoh H, Urano F, et al. Amyloid beta induces neuronal cell death through ROS-mediated ASK1 activation. Cell Death Differ 2005; 12: 19–24.

    Article  CAS  PubMed  Google Scholar 

  47. Molton SA, Todd DE, Cook SJ. Selective activation of the c-Jun N-terminal kinase (JNK) pathway fails to elicit Bax activation or apoptosis unless the phosphoinositide 3′-kinase (PI3K) pathway is inhibited. Oncogene 2003; 22: 4690–4701.

    Article  CAS  PubMed  Google Scholar 

  48. Oyadomari S, Mori M. Roles of CHOP/GADD153 in endoplasmic reticulum stress. Cell Death Differ 2004; 11: 381–389.

    Article  CAS  PubMed  Google Scholar 

  49. Kim DG, You KR, Liu MJ, Choi YK, Won YS. GADD153-mediated anticancer effects of N-(4-hydroxyphenyl)retinamide on human hepatoma cells. J Biol Chem 2002; 277: 38930–38938.

    CAS  PubMed  Google Scholar 

  50. Zinszner H, Kuroda M, Wang X, et al. CHOP is implicated in programmed cell death in response to impaired function of the endoplasmic reticulum. Genes Dev 1998; 12: 982–995.

    CAS  PubMed  Google Scholar 

  51. Fawcett TW, Martindale JL, Guyton KZ, Hai T, Holbrook NJ. 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 1999; 339: 135–141.

    Article  CAS  PubMed  Google Scholar 

  52. McCullough KD, Martindale JL, Klotz LO, Aw TY, Holbrook NJ. Gadd153 sensitizes cells to endoplasmic reticulum stress by down-regulating Bcl2 and perturbing the cellular redox state. Mol Cell Biol 2001; 21: 1249–1259.

    Article  CAS  PubMed  Google Scholar 

  53. Pugazhenthi S, Nesterova A, Sable C, et al. Akt/protein kinase B up-regulates Bcl-2 expression through cAMP-response element-binding protein. J Biol Chem 2000; 275: 10761–10766.

    Article  CAS  PubMed  Google Scholar 

  54. Gupta S, Yel L, Kim D, Kim C, Chiplunkar S, Gollapudi S. Arsenic trioxide induces apoptosis in peripheral blood T lymphocyte subsets by inducing oxidative stress: A role of Bcl-2. Mol Cancer Ther 2003; 2: 711–719.

    CAS  PubMed  Google Scholar 

  55. Egger L, Schneider J, Rheme C, Tapernoux M, Hacki J, Borner C. Serine proteases mediate apoptosis-like cell death and phagocytosis under caspase-inhibiting conditions. Cell Death Differ 2003; 10: 1188–1203.

    Article  CAS  PubMed  Google Scholar 

  56. Jimbo A, Fujita E, Kouroku Y, et al. ER stress induces caspase-8 activation, stimulating cytochrome c release and caspase-9 activation. Exp Cell Res 2003; 283: 156–166.

    Article  CAS  PubMed  Google Scholar 

  57. Southwood CM, Garbern J, Jiang W, Gow A. The unfolded protein response modulates disease severity in Pelizaeus-Merzbacher disease. Neuron 2002; 36: 585–596.

    Article  CAS  PubMed  Google Scholar 

  58. Berridge MJ. Calcium and oxidative stress: From cell signaling to cell death. Mol Immunol 2002; 38: 713–721.

    Google Scholar 

  59. Boehning D, Patterson RL, Snyder SH. Apoptosis and calcium: New roles for cytochrome c and inositol 1,4,5-trisphosphate. Cell Cycle 2004; 3: 252–254.

    CAS  PubMed  Google Scholar 

  60. Tantral L, Malathi K, Kohyama S, Silane M, Berenstein A, Jayaraman T. Intracellular calcium release is required for caspase-3 and -9 activation. Cell Biochem Funct 2004; 22: 35–40.

    Article  CAS  PubMed  Google Scholar 

  61. Ferrari D, Pinton P, Szabadkai G, et al. Endoplasmic reticulum, Bcl-2 and Ca2+ handling in apoptosis. Cell Calcium 2002; 32: 413–420.

    Article  CAS  PubMed  Google Scholar 

  62. Foyouzi-Youssefi R, Arnaudeau S, Borner C, et al. Bcl-2 decreases the free Ca2+ concentration within the endoplasmic reticulum. Proc Natl Acad Sci USA 2000; 97: 5723–5738.

    Article  CAS  PubMed  Google Scholar 

  63. Oakes SA, Opferman JT, Pozzan T, Korsmeyer SJ, Scorrano L. Regulation of endoplasmic reticulum Ca2+ dynamics by proapoptotic BCL-2 family members. Biochem Pharmacol 2003; 66: 1335–1340.

    Article  CAS  PubMed  Google Scholar 

  64. Rizzuto R, Pinton P, Ferrari D, et al. Calcium and apoptosis: Facts and hypotheses. Oncogene 2003; 22: 8619–8627.

    Article  CAS  PubMed  Google Scholar 

  65. Nutt LK, Chandra J, Pataer A, et al. Bax-mediated Ca2+ mobilization promotes cytochrome c release during apoptosis. J Biol Chem 2002; 277: 20301–29308.

    CAS  PubMed  Google Scholar 

  66. Zhu L, Ling S, Yu XD, et al. Modulation of mitochondrial Ca(2+) homeostasis by Bcl-2. J Biol Chem 1999; 274: 33267–33273.

    CAS  PubMed  Google Scholar 

  67. Germain M, Mathai JP, Shore GC. BH-3-only BIK functions at the endoplasmic reticulum to stimulate cytochrome c release from mitochondria. J Biol Chem 2002; 277: 18053–18060.

    Article  CAS  PubMed  Google Scholar 

  68. Shannon AM, Bouchier-Hayes DJ, Condron CM, Toomey D. Tumour hypoxia, chemotherapeutic resistance and hypoxia-related therapies. Cancer Treat Rev 2003; 29: 297–307.

    Article  CAS  PubMed  Google Scholar 

  69. Chen KD, Hung JJ, Huang HL, Chang MD, Lai YK. Rapid induction of the Grp78 gene by cooperative actions of okadaic acid and heat-shock in 9L rat brain tumor cells-involvement of a cAMP responsive element-like promoter sequence and a protein kinase A signaling pathway. Eur J Biochem 1997; 248: 120–129.

    CAS  PubMed  Google Scholar 

  70. Ramsay RG, Ciznadija D, Mantamadiotis T, Anderson R, Pearson R. Expression of stress response protein glucose regulated protein-78 mediated by c-Myb. Int J Biochem Cell Biol 2005; 37: 1254–1268.

    Article  CAS  PubMed  Google Scholar 

  71. Reddy RK, Mao C, Baumeister P, Austin RC, Kaufman RJ, Lee AS. Endoplasmic reticulum chaperone protein GRP78 protects cells from apoptosis induced by topoisomerase inhibitors: Role of ATP binding site in suppression of caspase-7 activation. J Biol Chem 2003; 278: 20915–20924.

    CAS  PubMed  Google Scholar 

  72. Comerford KM, Wallace TJ, Karhausen J, Louis NA, Montalto MC, Colgan SP. Hypoxia-inducible factor-1-dependent regulation of the multidrug resistance (MDR1) gene. Cancer Res 2002; 62: 3387–3394.

    CAS  PubMed  Google Scholar 

  73. Park HR, Tomida A, Sato S, et al. Effect on tumor cells of blocking survival response to glucose deprivation. J Natl Cancer Inst 2004; 96: 1300–1310.

    CAS  PubMed  Google Scholar 

  74. Voorhees PM, Dees EC, O'Neil B, Orlowski RZ. The proteasome as a target for cancer therapy. Clin Cancer Res 2003; 9: 6316–6325.

    CAS  PubMed  Google Scholar 

  75. Lenz HJ. Clinical update: Proteasome inhibitors in solid tumors. Cancer Treat Rev 2003; 29: 41–48.

    Article  CAS  PubMed  Google Scholar 

  76. Rajkumar SV, Richardson PG, Hideshima T, Anderson KC. Proteasome inhibition as a novel therapeutic target in human cancer. J Clin Oncol 2005; 23: 630–639.

    Article  CAS  PubMed  Google Scholar 

  77. Catley L, Tai YT, Shringarpure R, et al. Proteasomal degradation of topoisomerase I is preceded by c-Jun NH2-terminal kinase activation, Fas up-regulation, and poly(ADP-ribose) polymerase cleavage in SN38-mediated cytotoxicity against multiple myeloma. Cancer Res 2004; 64: 8746–8753.

    Article  CAS  PubMed  Google Scholar 

  78. Kamat AM, Karashima T, Davis DW, et al. The proteasome inhibitor bortezomib synergizes with gemcitabine to block the growth of human 253JB-V bladder tumors in vivo. Mol Cancer Ther 2004; 3: 279–290.

    CAS  PubMed  Google Scholar 

  79. Nawrocki ST, Sweeney-Gotsch B, Takamori R, McConkey DJ. The proteasome inhibitor bortezomib enhances the activity of docetaxel in orthotopic human pancreatic tumor xenografts. Mol Cancer Ther 2004; 3: 59–70.

    CAS  PubMed  Google Scholar 

  80. Cusack JC. Rationale for the treatment of solid tumors with the proteasome inhibitor bortezomib. Cancer Treat Rev 2003; 29: 21–31.

    Article  CAS  PubMed  Google Scholar 

  81. Nozaki S, Sledge Jr GW, Nakshatri H. Repression of GADD153/CHOP by NF-kappaB: A possible cellular defense against endoplasmic reticulum stress-induced cell death. Oncogene 2001; 20: 2178–2185.

    Article  CAS  PubMed  Google Scholar 

  82. Kim R, Ohi Y, Inoue H, Aogi K, Toge T. Introduction of gadd153 gene into gastric cancer cells can modulate sensitivity to anticancer agents in association with apoptosis. Anticancer Res 1999; 19: 1779–1783.

    CAS  PubMed  Google Scholar 

  83. Kim R, Ohi Y, Inoue H, Toge T. Taxotere activates transcription factor AP-1 in association with apoptotic cell death in gastric cancer cell lines. Anticancer Res 1999; 19: 5399–5405.

    CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. International Radiation Information Center, Research Institute for Radiation Biology and Medicine, Hiroshima University, Hiroshima, Japan

    R. Kim

  2. Departent of Surgical Oncology, Research Institute for Radiation Biology and Medicine, Hiroshima University, Hiroshima, Japan

    M. Emi, K. Tanabe & S. Murakami

  3. International Radiation Information Center, Research Institute for Radiation Biology and Medicine, Hiroshima University, 1-2-3 Kasumi Minami-ku, Hiroshima, 734-8553, Japan

    R. Kim

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Kim, R., Emi, M., Tanabe, K. et al. Role of the unfolded protein response in cell death. Apoptosis 11, 5–13 (2006). https://doi.org/10.1007/s10495-005-3088-0

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