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XIAP as a multifaceted molecule in Cellular Signaling

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Abstract

XIAP, X-linked inhibitor of apoptosis protein, is a member of the inhibitor of apoptosis protein (IAP) family known for its important conserved inhibitory effect on caspase activity. Since the introduction of XIAP almost three decades ago, numerous experimental studies have been performed for a wide range of cellular pathways and mechanisms. In this perspective, we summarize key trends of XIAP as an important regulator of cellular signaling. Experimental research indicates that XIAP as a key molecule of cell death not only suppress caspases and apoptosis, but also regulates inflammatory signaling, mitogenic kinase signaling, cell proliferation as well as cell invasion and metastasis. In this review, we provide basic knowledge of the roles of XIAP, explain its role in necroptosis, anoikis, autophagy and neuronal differentiation. XIAP is involved in regulating intracellular ROS production and copper homeostasis which this review focuses on. A different face of XIAP in response to DNA damage and chronic ER stress is also discussed.

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References

  1. Kerr JF, Wyllie AH, Currie AR (1972) Apoptosis: a basic biological phenomenon with wideranging implications in tissue kinetics. Br J Cancer 26:239–257

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Mehdizadeh K, Ataei F, Hosseinkhani S (2021) Treating MCF7 breast cancer cell with proteasome inhibitor Bortezomib restores apoptotic factors and sensitizes cell to Docetaxel. Med Oncol 38:1–8

    Article  CAS  Google Scholar 

  3. Peter ME, Heufelder AE, Hengartner MO (1997) Advances in apoptosis research. Proc Natl Acad Sci U S A 94:12736–12737

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Mehdizadeh K, Ataei F, Hosseinkhani S (2020) Effects of doxorubicin and docetaxel on susceptibility to apoptosis in high expression level of survivin in HEK and HEK-S cell lines as in vitro models. Biochem Biophys Res Commun 532:139–144

    Article  CAS  PubMed  Google Scholar 

  5. Nuñez G, Benedict MA, Hu Y, Inohara N (1998) Caspases: the proteases of the apoptotic pathway. Oncogene 17:3237–3245

    Article  PubMed  Google Scholar 

  6. Bakhshoudeh M, Mehdizadeh K, Hosseinkhani S, Ataei F (2021) Upregulation of apoptotic protease activating factor-1 expression correlates with anti-tumor effect of taxane drug. Med Oncol 38:88–95

    Article  CAS  PubMed  Google Scholar 

  7. Deveraux QL, Roy N, Stennicke HR et al (1998) IAPs block apoptotic events induced by caspase-8 and cytochrome c by direct inhibition of distinct caspases. EMBO J 17:2215–2223

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Houshdarpour R, Ataei F, Hosseinkhani S (2021) Efficient stable cell line generation of survivin as an in vitro model for specific functional analysis in apoptosis and drug screening. Mol Biotechnol 63:515–524

    Article  CAS  PubMed  Google Scholar 

  9. Karimzadeh S, Hosseinkhani S, Fathi A, Ataei F, Baharvand H (2018) Insufficient Apaf-1 expression in early stages of neural differentiation of human embryonic stem cells might protect them from apoptosis. Eur J Cell Biol 97:126–135

    Article  CAS  PubMed  Google Scholar 

  10. Suzuki Y, Nakabayashi Y, Nakata K, Reed JC, Takahashi R (2001) X-linked inhibitor of apoptosis protein (XIAP) inhibits caspase-3 and-7 in distinct modes. J Biol Chem 276:27058–27063

    Article  CAS  PubMed  Google Scholar 

  11. Deveraux QL, Reed JC (1999) IAP family proteins—suppressors of apoptosis. Genes Dev 13:239–252

    Article  CAS  PubMed  Google Scholar 

  12. Tu H, Costa M (2020) XIAP’s Profile in human cancer. Biomolecules 10:1493

    Article  CAS  PubMed Central  Google Scholar 

  13. Wilkinson JC, Wilkinson AS, Galbán S, Csomos RA, Duckett CS (2008) Apoptosis-inducing factor is a target for ubiquitination through interaction with XIAP. Mol Cell Biol 28:237–247

    Article  CAS  PubMed  Google Scholar 

  14. Listen P, Roy N, Tamai K et al (1996) Suppression of apoptosis in mammalian cells by NAIP and a related family of IAP genes. Nature 379:349–353

    Article  Google Scholar 

  15. Birnbaum M, Clem R, Miller L (1994) An apoptosis-inhibiting gene from a nuclear polyhedrosis virus encoding a polypeptide with Cys/His sequence motifs. J Virol 68:2521–2528

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Hinds MG, Norton RS, Vaux DL, Day CL (1999) Solution structure of a baculoviral inhibitor of apoptosis (IAP) repeat. Nat Struct Biol 6:648–651

    Article  CAS  PubMed  Google Scholar 

  17. Yang Y, Fang S, Jensen JP, Weissman AM, Ashwell JD (2000) Ubiquitin protein ligase activity of IAPs and their degradation in proteasomes in response to apoptotic stimuli. Science 288:874–877

    Article  CAS  PubMed  Google Scholar 

  18. Gyrd-Hansen M, Darding M, Miasari M et al (2008) IAPs contain an evolutionarily conserved ubiquitin-binding domain that regulates NF-κB as well as cell survival and oncogenesis. Nat Cell Biol 10:1309–1317

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Blankenship JW, Varfolomeev E, Goncharov T et al (2009) Ubiquitin binding modulates IAP antagonist-stimulated proteasomal degradation of c-IAP1 and c-IAP2. Biochem J 417:149–165

    Article  CAS  PubMed  Google Scholar 

  20. Deveraux QL, Leo E, Stennicke HR, Welsh K, Salvesen GS, Reed JC (1999) Cleavage of human inhibitor of apoptosis protein XIAP results in fragments with distinct specificities for caspases. EMBO J 18:5242–5251

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Eckelman BP, Salvesen GS, Scott FL (2006) Human inhibitor of apoptosis proteins: why XIAP is the black sheep of the family. EMBO Rep 7:988–994

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Scott FL, Denault JB, Riedl SJ, Shin H, Renatus M, Salvesen GS (2005) XIAP inhibits caspase-3 and‐7 using two binding sites: evolutionarily conserved mechanism of IAPs. EMBO J 24:645–655

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Sun C, Cai M, Gunasekera AH et al (1999) NMR structure and mutagenesis of the inhibitor-of-apoptosis protein XIAP. Nature 401:818–822

    Article  CAS  PubMed  Google Scholar 

  24. Fraser AG, James C, Evan GI, Hengartner MO (1999) Caenorhabditis elegans inhibitor of apoptosis protein (IAP) homologue BIR-1 plays a conserved role in cytokinesis. Curr Biol 9:292–302

    Article  CAS  PubMed  Google Scholar 

  25. Uren AG, Beilharz T, O’Connell MJ et al (1999) Role for yeast inhibitor of apoptosis (IAP)-like proteins in cell division. Proc Natl Acad Sci U S A 96:10170–10175

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Fuchs Y, Steller H (2011) Programmed cell death in animal development and disease. Cell 147:742–758

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Vasudevan D, Ryoo HD (2015) Regulation of cell death by IAPs and their antagonists. Crr Top Dev Biol 114:185–208

    Article  CAS  Google Scholar 

  28. White K, Grether ME, Abrams JM, Young L, Farrell K, Steller H (1994) Genetic control of programmed cell death in Drosophila. Sci 264:677–683

    Article  CAS  Google Scholar 

  29. Grether ME, Abrams JM, Agapite J, White K, Steller H (1995) The head involution defective gene of Drosophila melanogaster functions in programmed cell death. Genes Dev 9:1694–1708

    Article  CAS  PubMed  Google Scholar 

  30. Chen P, Nordstrom W, Gish B, Abrams JM (1996) grim, a novel cell death gene in Drosophila. Genes Dev 10:1773–1782

    Article  CAS  PubMed  Google Scholar 

  31. Goyal L, McCall K, Agapite J, Hartwieg E, Steller H (2000) Induction of apoptosis by Drosophila reaper, hid and grim through inhibition of IAP function. EMBO J 19:589–597

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Du C, Fang M, Li Y, Li L, Wang X (2000) Smac, a mitochondrial protein that promotes cytochrome c–dependent caspase activation by eliminating IAP inhibition. Cell 102:33–42

    Article  CAS  PubMed  Google Scholar 

  33. Verhagen AM, Ekert PG, Pakusch M et al (2000) Identification of DIABLO, a mammalian protein that promotes apoptosis by binding to and antagonizing IAP proteins. Cell 102:43–53

    Article  CAS  PubMed  Google Scholar 

  34. Hegde R, Srinivasula SM, Zhang Z et al (2002) Identification of Omi/HtrA2 as a mitochondrial apoptotic serine protease that disrupts inhibitor of apoptosis protein-caspase interaction. J Biol Chem 277:432–438

    Article  CAS  PubMed  Google Scholar 

  35. Schile AJ, García-Fernández M, Steller H (2008) Regulation of apoptosis by XIAP ubiquitin-ligase activity. Genes Dev 22:2256–2266

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Qin S, Yang C, Zhang B et al (2016) XIAP inhibits mature Smac-induced apoptosis by degrading it through ubiquitination in NSCLC. Int J Oncol 49:1289–1296

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Suzuki Y, Nakabayashi Y, Takahashi R (2001) Ubiquitin-protein ligase activity of X-linked inhibitor of apoptosis protein promotes proteasomal degradation of caspase-3 and enhances its anti-apoptotic effect in Fas-induced cell death. Proc Natl Acad Sci U S A9 8:8662–8667

    Article  Google Scholar 

  38. Shin H, Okada K, Wilkinson JC et al (2003) Identification of ubiquitination sites on the X-linked inhibitor of apoptosis protein. Biochem J 373:965–971

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Frisch SM, Francis H (1994) Disruption of epithelial cell-matrix interactions induces apoptosis. J Cell Biol 124:619–626

    Article  CAS  PubMed  Google Scholar 

  40. Taddei M, Giannoni E, Fiaschi T, Chiarugi P (2012) Anoikis: an emerging hallmark in health and diseases. J Pathol 226:380–393

    Article  CAS  PubMed  Google Scholar 

  41. Guicciardi ME, Gores GJ (2009) Life and death by death receptors. FASEB 23:1625–1637

    Article  CAS  Google Scholar 

  42. Chiarugi P, Giannoni E (2008) Anoikis: a necessary death program for anchorage-dependent cells. Biochem Pharmacol 76:1352–1364

    Article  CAS  PubMed  Google Scholar 

  43. Marconi A, Atzei P, Panza C et al (2004) FLICE/caspase-8 activation triggers anoikis induced by β1-integrin blockade in human keratinocytes. J Cell Sci 117:5815–5823

    Article  CAS  PubMed  Google Scholar 

  44. Aoudjit F, Vuori K (2001) Matrix attachment regulates Fas-induced apoptosis in endothelial cells: a role for c-flip and implications for anoikis. J Cell Biol 152:633–644

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. García-Fernández M, Kissel H, Brown S et al (2010) Sept4/ARTS is required for stem cell apoptosis and tumor suppression. Genes Dev 24:2282–2293

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  46. Gottfried Y, Rotem A, Lotan R, Steller H, Larisch S (2004) The mitochondrial ARTS protein promotes apoptosis through targeting XIAP. EMBO J 23:1627–1635

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Liu Z, Li H, Wu X et al (2006) Detachment-induced upregulation of XIAP and cIAP2 delays anoikis of intestinal epithelial cells. Oncogene 25:7680–7690

    Article  CAS  PubMed  Google Scholar 

  48. Stehlik C, De Martin R, Kumabashiri I, Schmid JA, Binder BR, Lipp J (1998) Nuclear factor (NF)-κB–regulated X-chromosome–linked iap gene expression protects endothelial cells from tumor necrosis factor α–induced apoptosis. J Exp Med 188:211–216

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Biswas DK, Martin KJ, McAlister C et al (2003) Apoptosis caused by chemotherapeutic inhibition of nuclear factor-κB activation. Cancer Res 63:290–295

    CAS  PubMed  Google Scholar 

  50. Yamakita Y, Totsukawa G, Yamashiro S et al (1999) Dissociation of FAK/p130CAS/c-Src complex during mitosis: role of mitosis-specific serine phosphorylation of FAK. Cancer Res 144:315–324

    CAS  Google Scholar 

  51. Ikeda H, Suzuki Y, Suzuki M et al (1998) Apoptosis is a major mode of cell death caused by ischaemia and ischaemia/reperfusion injury to the rat intestinal epithelium. Gut 42:530–537

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Levine B, Klionsky DJ (2004) Development by self-digestion: molecular mechanisms and biological functions of autophagy. Dev Cell 6:463–477

    Article  CAS  PubMed  Google Scholar 

  53. Klionsky DJ (2007) Autophagy: from phenomenology to molecular understanding in less than a decade. Nat Rev Mol Cell Biol 8:931–937

    Article  CAS  PubMed  Google Scholar 

  54. Lum JJ, DeBerardinis RJ, Thompson CB (2005) Autophagy in metazoans: cell survival in the land of plenty. Nat Rev Mol Cell Biol 6:439–448

    Article  CAS  PubMed  Google Scholar 

  55. Mathew R, Karantza-Wadsworth V, White E (2007) Role of autophagy in cancer. Nat Rev Cancer 7:961–967

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Mah LY, Ryan KM (2012) Autophagy and cancer. Cold Spring Harb Perspect Biol 4:a008821

    Article  PubMed  PubMed Central  Google Scholar 

  57. Huang X, Wu Z, Mei Y, Wu M (2013) XIAP inhibits autophagy via XIAP-Mdm2‐p53 signalling. EMBO J 32:2204–2216

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Itahana K, Mao H, Jin A et al (2007) Targeted inactivation of Mdm2 RING finger E3 ubiquitin ligase activity in the mouse reveals mechanistic insights into p53 regulation. Cancer Cell 12:355–366

    Article  CAS  PubMed  Google Scholar 

  59. Maiuri MC, Galluzzi L, Morselli E, Kepp O, Malik SA, Kroemer G (2010) Autophagy regulation by p53. Curr Opin Cell Biol 22:181–185

    Article  CAS  PubMed  Google Scholar 

  60. Tasdemir E, Maiuri MC, Galluzzi L et al (2008) Regulation of autophagy by cytoplasmic p53. Nat Cell Biol 10:676–687

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Gao X, Zhang L, Wei Y et al (2019) Prognostic value of XIAP level in patients with various cancers: a systematic review and meta-analysis. J Cancer 10:1528

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Pasparakis M, Vandenabeele P (2015) Necroptosis and its role in inflammation. Nature 517:311–320

    Article  CAS  PubMed  Google Scholar 

  63. Wang X, Yousefi S, Simon H-U (2018) Necroptosis and neutrophil-associated disorders. Cell Death Dis 9:1–9

    CAS  Google Scholar 

  64. Damgaard RB, Nachbur U, Yabal M et al (2012) The ubiquitin ligase XIAP recruits LUBAC for NOD2 signaling in inflammation and innate immunity. Mol cell 46:746–758

    Article  CAS  PubMed  Google Scholar 

  65. Lawlor KE, Khan N, Mildenhall A et al (2015) RIPK3 promotes cell death and NLRP3 inflammasome activation in the absence of MLKL. Nat Commun 6:1–19

    Article  CAS  Google Scholar 

  66. Yabal M, Müller N, Adler H et al (2014) XIAP restricts TNF-and RIP3-dependent cell death and inflammasome activation. Cell Rep 7:1796–1808

    Article  CAS  PubMed  Google Scholar 

  67. Vandenabeele P, Galluzzi L, Berghe TV, Kroemer G (2010) Molecular mechanisms of necroptosis: an ordered cellular explosion. Nat Rev Mol Cell Biol 11:700–714

    Article  CAS  PubMed  Google Scholar 

  68. Silke J, Rickard JA, Gerlic M (2015) The diverse role of RIP kinases in necroptosis and inflammation. Nat Immunol 16:689–697

    Article  CAS  PubMed  Google Scholar 

  69. Murphy JM, Czabotar PE, Hildebrand JM et al (2013) The pseudokinase MLKL mediates necroptosis via a molecular switch mechanism. Immunity 39:443–453

    Article  CAS  PubMed  Google Scholar 

  70. Gyrd-Hansen M, Meier P (2010) IAPs: from caspase inhibitors to modulators of NF-κB, inflammation and cancer. Nat Rev Cancer 10:561–574

    Article  CAS  PubMed  Google Scholar 

  71. Wicki S, Gurzeler U, Wong WW-L, Jost PJ, Bachmann D, Kaufmann T (2016) Loss of XIAP facilitates switch to TNF α-induced necroptosis in mouse neutrophils. Cell Death Dis 7:e2422–e2422

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  72. Weinlich R, Oberst A, Beere HM, Green DR (2017) Necroptosis in development, inflammation and disease. Nat Rev Mol Cell Biol 18:127–136

    Article  CAS  PubMed  Google Scholar 

  73. Tenev T, Bianchi K, Darding M et al (2011) The Ripoptosome, a signaling platform that assembles in response to genotoxic stress and loss of IAPs. Mol cell 43:432–448

    Article  CAS  PubMed  Google Scholar 

  74. Moulin M, Anderton H, Voss AK et al (2012) IAPs limit activation of RIP kinases by TNF receptor 1 during development. EMBO J 31:1679–1691

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  75. He S, Liang Y, Shao F, Wang X (2011) Toll-like receptors activate programmed necrosis in macrophages through a receptor-interacting kinase-3–mediated pathway. Proceedings of the Natl Acad Sci 108:20054–20059

  76. Fadó R, Moubarak RS, Miñano-Molina AJ et al (2013) X-linked inhibitor of apoptosis protein negatively regulates neuronal differentiation through interaction with cRAF and Trk. Sci rep 3:1–11

    Article  Google Scholar 

  77. Yamaguchi K, Nagai Si, Ninomiya-Tsuji J et al (1999) XIAP, a cellular member of the inhibitor of apoptosis protein family, links the receptors to Tables 1–TAK1 in the BMP signaling pathway. EMBO J 18:179–187

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  78. Olayioye M, Kaufmann H, Pakusch M, Vaux D, Lindeman G, Visvader J (2005) XIAP-deficiency leads to delayed lobuloalveolar development in the mammary gland. Cell Death Differ 12:87–90

    Article  CAS  PubMed  Google Scholar 

  79. Dogan T, Harms GS, Hekman M et al (2008) X-linked and cellular IAPs modulate the stability of C-RAF kinase and cell motility. Nat cell biol 10:1447–1455

    Article  CAS  PubMed  Google Scholar 

  80. Heiman MG, Shaham S (2010) Twigs into branches: how a filopodium becomes a dendrite. Curr Opin Neurobiol 20:86–91

    Article  CAS  PubMed  Google Scholar 

  81. Moubarak RS, Solé C, Pascual M et al (2010) The death receptor antagonist FLIP-L interacts with Trk and is necessary for neurite outgrowth induced by neurotrophins. J Neurosci 30:6094–6105

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  82. Liu J, Zhang D, Luo W et al (2011) X-linked inhibitor of apoptosis protein (XIAP) mediates cancer cell motility via Rho GDP dissociation inhibitor (RhoGDI)-dependent regulation of the cytoskeleton. J Biol Chem 286:15630–15640

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  83. Benhar M, Engelberg D, Levitzki A (2002) ROS, stress-activated kinases and stress signaling in cancer. EMBO Rep 3:420–425

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  84. Barnham KJ, Masters CL, Bush AI (2004) Neurodegenerative diseases and oxidative stress. Nat Rev Drug Discov 3:205–214

    Article  CAS  PubMed  Google Scholar 

  85. Resch U, Schichl YM, Sattler S, de Martin R (2008) XIAP regulates intracellular ROS by enhancing antioxidant gene expression. Biochem Biophys Res Commun 375:156–161

    Article  CAS  PubMed  Google Scholar 

  86. Gabbita SP, Robinson KA, Stewart CA, Floyd RA, Hensley K (2000) Redox regulatory mechanisms of cellular signal transduction. Arch Biochem Biophys 376:1–13

    Article  CAS  PubMed  Google Scholar 

  87. Jaiswal AK (2004) Nrf2 signaling in coordinated activation of antioxidant gene expression. Free Radic Biol Med 36:1199–1207

    Article  CAS  PubMed  Google Scholar 

  88. Ueda S, Masutani H, Nakamura H, Tanaka T, Ueno M, Yodoi J (2002) Redox control of cell death. Antioxid Redox Signal 4:405–414

    Article  CAS  PubMed  Google Scholar 

  89. Kamata H, Honda S-i, Maeda S, Chang L, Hirata H, Karin M (2005) Reactive oxygen species promote TNFα-induced death and sustained JNK activation by inhibiting MAP kinase phosphatases. Cell 120:649–661

    Article  CAS  PubMed  Google Scholar 

  90. Nguyen T, Sherratt PJ, Pickett CB (2003) Regulatory mechanisms controlling gene expression mediated by the antioxidant response element. Annu Rev Pharmacol Toxicol 43:233–260

    Article  CAS  PubMed  Google Scholar 

  91. Rushmore TH, Morton MR, Pickett CB (1991) The antioxidant responsive element. Activation by oxidative stress and identification of the DNA consensus sequence required for functional activity. J Biol Chem 266:11632–11639

    Article  CAS  PubMed  Google Scholar 

  92. Lu M, Lin S-C, Huang Y et al (2007) XIAP induces NF-κB activation via the BIR1/Table 1 interaction and BIR1 dimerization. Mol cell 26:689–702

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  93. Lewis S, Holcik M (2005) IRES in distress: translational regulation of the inhibitor of apoptosis proteins XIAP and HIAP2 during cell stress. Cell Death Differ 12:547–553

    Article  CAS  PubMed  Google Scholar 

  94. Kucharczak J, Simmons MJ, Fan Y, Gelinas C (2003) To be, or not to be: NF-κ B is the answer–role of Rel/NF-κ B in the regulation of apoptosis. Oncogene 22:8961–8982

    Article  CAS  PubMed  Google Scholar 

  95. Puig S, Thiele DJ (2002) Molecular mechanisms of copper uptake and distribution. Curr Opin Chem Biol 6:171–180

    Article  CAS  PubMed  Google Scholar 

  96. Tao TY, Liu F, Klomp L, Wijmenga C, Gitlin JD (2003) The copper toxicosis gene product Murr1 directly interacts with the Wilson disease protein. J Biol Chem 278:41593–41596

    Article  CAS  PubMed  Google Scholar 

  97. Burstein E, Ganesh L, Dick RD et al (2004) A novel role for XIAP in copper homeostasis through regulation of MURR1. EMBO J 23:244–254

    Article  CAS  PubMed  Google Scholar 

  98. Fanciulli M, Bruno T, Padova MD et al (2000) Identification of a novel partner of RNA polymerase II subunit 11, Che-1, which interacts with and affects the growth suppression function of Rb. FASEB J 14:904–912

    Article  CAS  PubMed  Google Scholar 

  99. Bruno T, De Angelis R, De Nicola F et al (2002) Che-1 affects cell growth by interfering with the recruitment of HDAC1 by Rb. Cancer Cell 2:387–399

    Article  CAS  PubMed  Google Scholar 

  100. Bruno T, Iezzi S, De Nicola F et al (2008) Che-1 activates XIAP expression in response to DNA damage. Cell Death Differ 15:515–520

    Article  CAS  PubMed  Google Scholar 

  101. Bruno T, De Nicola F, Iezzi S et al (2006) Che-1 phosphorylation by ATM/ATR and Chk2 kinases activates p53 transcription and the G2/M checkpoint. Cancer Cell 10:473–486

    Article  CAS  PubMed  Google Scholar 

  102. Bruno T (2007) Che-1 phosphorylation by ATM/ATR and CHK2 kinases activates p53 transcription and the g2/m checkpoint. AACR 67:1079

    Google Scholar 

  103. Walter P, Ron D (2011) The unfolded protein response: from stress pathway to homeostatic regulation. Science 334:1081–1086

    Article  CAS  PubMed  Google Scholar 

  104. Tabas I, Ron D (2011) Integrating the mechanisms of apoptosis induced by endoplasmic reticulum stress. Nat cell biol 13:184–190

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  105. Hiramatsu N, Messah C, Han J, LaVail MM, Kaufman RJ, Lin JH (2014) Translational and posttranslational regulation of XIAP by eIF2α and ATF4 promotes ER stress–induced cell death during the unfolded protein response. Mol biol cell 25:1411–1420

    Article  PubMed  PubMed Central  Google Scholar 

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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  107. Reimertz C, Kögel D, Rami A, Chittenden T, 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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  108. Warnakulasuriyarachchi D, Cerquozzi S, Cheung HH, Holcík M (2004) Translational induction of the inhibitor of apoptosis protein HIAP2 during endoplasmic reticulum stress attenuates cell death and is mediated via an inducible internal ribosome entry site element. J Biol Chem 279:17148–17157

    Article  CAS  PubMed  Google Scholar 

  109. Muaddi H, Majumder M, Peidis P et al (2010) Phosphorylation of eIF2α at serine 51 is an important determinant of cell survival and adaptation to glucose deficiency. Mol biol cell 21:3220–3231

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

This work was supported by the research council of Tarbiat Modares University.

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This article was funded by the research council of Tarbiat Modares University.

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  1. Department of Biochemistry, Faculty of Biological Sciences, Trabiat Modares University, Tehran, Iran

    Mina Hanifeh & Farangis Ataei

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  1. Mina Hanifeh
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MH wrote the first draft of the manuscript. FA edited and finalized the manuscript. MH and FA generated all figures and all structures.

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Hanifeh, M., Ataei, F. XIAP as a multifaceted molecule in Cellular Signaling. Apoptosis 27, 441–453 (2022). https://doi.org/10.1007/s10495-022-01734-z

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