Cells are constantly exposed to endogenous and exogenous cellular injuries. They cope with stressful stimuli by adapting their metabolism and activating various “guardian molecules.” These pro-survival factors protect essential cell constituents, prevent cell death, and possibly repair cellular damages. The Inhibitor of Apoptosis (IAPs) proteins display both anti-apoptotic and pro-survival properties and their expression can be induced by a variety of cellular stress such as hypoxia, endoplasmic reticular stress and DNA damage. Thus, IAPs can confer tolerance to cellular stress. This review presents the anti-apoptotic and survival functions of IAPs and their role in the adaptive response to cellular stress. The involvement of IAPs in human physiology and diseases in connection with a breakdown of cellular homeostasis will be discussed.
References
[1]
Dubrez-Daloz, L.; Dupoux, A.; Cartier, J. IAPs: More than just inhibitors of apoptosis proteins. Cell. Cycle 2008, 7, 1036–1046, doi:10.4161/cc.7.8.5783.
[2]
Gyrd-Hansen, M.; Meier, P. IAPs: From caspase inhibitors to modulators of NF-kappaB, inflammation and cancer. Nat. Rev. Cancer 2010, 10, 561–574, doi:10.1038/nrc2889.
[3]
Beug, S.T.; Cheung, H.H.; Lacasse, E.C.; Korneluk, R.G. Modulation of immune signalling by inhibitors of apoptosis. Trends Immunol. 2012. in press.
[4]
Warnakulasuriyarachchi, D.; Cerquozzi, S.; Cheung, H.H.; Holcik, M. 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. 2004, 279, 17148–17157, doi:10.1074/jbc.M308737200.
[5]
Van Eden, M.E.; Byrd, M.P.; Sherrill, K.W.; Lloyd, R.E. Translation of cellular inhibitor of apoptosis protein 1 (c-IAP1) mRNA is IRES mediated and regulated during cell stress. RNA 2004, 10, 469–481, doi:10.1261/rna.5156804.
[6]
Holcik, M.; Lefebvre, C.; Yeh, C.; Chow, T.; Korneluk, R.G. A new internal-ribosome-entry-site motif potentiates XIAP-mediated cytoprotection. Nat. Cell. Biol. 1999, 1, 190–192, doi:10.1038/11109.
[7]
Eckelman, B.P.; Drag, M.; Snipas, S.J.; Salvesen, G.S. The mechanism of peptide-binding specificity of IAP BIR domains. Cell. Death Differ. 2008, 15, 920–928, doi:10.1038/cdd.2008.6.
[8]
Vucic, D.; Dixit, V.M.; Wertz, I.E. Ubiquitylation in apoptosis: a post-translational modification at the edge of life and death. Nat. Rev. Mol. Cell. Biol. 2011, 12, 439–452, doi:10.1038/nrm3143.
[9]
Silke, J.; Kratina, T.; Chu, D.; Ekert, P.G.; Day, C.L.; Pakusch, M.; Huang, D.C.; Vaux, D.L. Determination of cell survival by RING-mediated regulation of inhibitor of apoptosis (IAP) protein abundance. Proc. Natl. Acad. Sci. USA 2005, 102, 16182–16187.
[10]
Mace, P.D.; Linke, K.; Feltham, R.; Schumacher, F.R.; Smith, C.A.; Vaux, D.L.; Silke, J.; Day, C.L. Structures of the cIAP2 RING domain reveal conformational changes associated with ubiquitin-conjugating enzyme (E2) recruitment. J. Biol. Chem. 2008, 283, 31633–31640.
[11]
Cheung, H.H.; Plenchette, S.; Kern, C.J.; Mahoney, D.J.; Korneluk, R.G. The RING domain of cIAP1 mediates the degradation of RING-bearing inhibitor of apoptosis proteins by distinct pathways. Mol. Biol. Cell. 2008, 19, 2729–2740, doi:10.1091/mbc.E08-01-0107.
[12]
Rajalingam, K.; Sharma, M.; Paland, N.; Hurwitz, R.; Thieck, O.; Oswald, M.; Machuy, N.; Rudel, T. IAP-IAP complexes required for apoptosis resistance of C. trachomatis-infected cells. PLoS Pathog. 2006, 2, e114, doi:10.1371/journal.ppat.0020114.
Yang, Y.; Fang, S.; Jensen, J.P.; Weissman, A.M.; Ashwell, J.D. Ubiquitin protein ligase activity of IAPs and their degradation in proteasomes in response to apoptotic stimuli. Science 2000, 288, 874–877, doi:10.1126/science.288.5467.874.
[15]
Hao, Y.; Sekine, K.; Kawabata, A.; Nakamura, H.; Ishioka, T.; Ohata, H.; Katayama, R.; Hashimoto, C.; Zhang, X.; Noda, T.; et al. Apollon ubiquitinates SMAC and caspase-9, and has an essential cytoprotection function. Nat. Cell. Biol. 2004, 6, 849–860, doi:10.1038/ncb1159.
[16]
Blankenship, J.W.; Varfolomeev, E.; Goncharov, T.; Fedorova, A.V.; Kirkpatrick, D.S.; Izrael-Tomasevic, A.; Phu, L.; Arnott, D.; Aghajan, M.; Zobel, K.; et al. Ubiquitin binding modulates IAP antagonist-stimulated proteasomal degradation of c-IAP1 and c-IAP2(1). Biochem. J. 2009, 417, 149–160, doi:10.1042/BJ20081885.
[17]
Gyrd-Hansen, M.; Darding, M.; Miasari, M.; Santoro, M.M.; Zender, L.; Xue, W.; Tenev, T.; da Fonseca, P.C.; Zvelebil, M.; Bujnicki, J.M.; et al. IAPs contain an evolutionarily conserved ubiquitin-binding domain that regulates NF-kappaB as well as cell survival and oncogenesis. Nat. Cell. Biol. 2008, 10, 1309–1317, doi:10.1038/ncb1789.
[18]
Lopez, J.; John, S.W.; Tenev, T.; Rautureau, G.J.; Hinds, M.G.; Francalanci, F.; Wilson, R.; Broemer, M.; Santoro, M.M.; Day, C.L.; et al. CARD-mediated autoinhibition of cIAP1's E3 ligase activity suppresses cell proliferation and migration. Mol. Cell. 2011, 42, 569–583, doi:10.1016/j.molcel.2011.04.008.
[19]
Roy, N.; Mahadevan, M.S.; McLean, M.; Shutler, G.; Yaraghi, Z.; Farahani, R.; Baird, S.; Besner-Johnston, A.; Lefebvre, C.; Kang, X.; et al. The gene for neuronal apoptosis inhibitory protein is partially deleted in individuals with spinal muscular atrophy. Cell 1995, 80, 167–178, doi:10.1016/0092-8674(95)90461-1.
[20]
Fulda, S.; Vucic, D. Targeting IAP proteins for therapeutic intervention in cancer. Nat. Rev. Drug Discov. 2012, 11, 109–124, doi:10.1038/nrd3627.
[21]
Pop, C.; Salvesen, G.S. Human caspases: Activation, specificity, and regulation. J. Biol. Chem. 2009, 284, 21777–21781, doi:10.1074/jbc.R800084200.
[22]
Mace, P.D.; Riedl, S.J. Molecular cell death platforms and assemblies. Curr. Opin. Cell. Biol. 2010, 22, 828–836, doi:10.1016/j.ceb.2010.08.004.
[23]
Wurstle, M.L.; Laussmann, M.A.; Rehm, M. The central role of initiator caspase-9 in apoptosis signal transduction and the regulation of its activation and activity on the apoptosome. Exp. Cell. Res. 2012, 318, 121–320.
[24]
Feoktistova, M.; Geserick, P.; Kellert, B.; Dimitrova, D.P.; Langlais, C.; Hupe, M.; Cain, K.; MacFarlane, M.; Hacker, G.; Leverkus, M. cIAPs block Ripoptosome formation, a RIP1/caspase-8 containing intracellular cell death complex differentially regulated by cFLIP isoforms. Mol. Cell. 2011, 43, 449–463, doi:10.1016/j.molcel.2011.06.011.
[25]
Tenev, T.; Bianchi, K.; Darding, M.; Broemer, M.; Langlais, C.; Wallberg, F.; Zachariou, A.; Lopez, J.; MacFarlane, M.; Cain, K.; et al. The Ripoptosome, a signaling platform that assembles in response to genotoxic stress and loss of IAPs. Mol. Cell. 2011, 43, 432–448.
[26]
Bertrand, M.J.; Vandenabeele, P. The Ripoptosome: Death decision in the cytosol. Mol. Cell. 2011, 43, 323–325, doi:10.1016/j.molcel.2011.07.007.
[27]
Cheung, H.H.; Lynn Kelly, N.; Liston, P.; Korneluk, R.G. Involvement of caspase-2 and caspase-9 in endoplasmic reticulum stress-induced apoptosis: A role for the IAPs. Exp. Cell. Res. 2006, 312, 2347–2357, doi:10.1016/j.yexcr.2006.03.027.
[28]
Imre, G.; Heering, J.; Takeda, A.N.; Husmann, M.; Thiede, B.; zu Heringdorf, D.M.; Green, D.R.; van der Goot, F.G.; Sinha, B. Caspase-2 is an initiator caspase responsible for pore-forming toxin-mediated apoptosis. EMBO J. 2012, 31, 2615–2628, doi:10.1038/emboj.2012.93.
[29]
Upton, J.P.; Austgen, K.; Nishino, M.; Coakley, K.M.; Hagen, A.; Han, D.; Papa, F.R.; Oakes, S.A. Caspase-2 cleavage of BID is a critical apoptotic signal downstream of endoplasmic reticulum stress. Mol. Cell. Biol. 2008, 28, 3943–3951, doi:10.1128/MCB.00013-08.
[30]
Shi, Y. A conserved tetrapeptide motif: Potentiating apoptosis through IAP-binding. Cell. Death Differ. 2002, 9, 93–95.
[31]
Hu, S.; Yang, X. Cellular inhibitor of apoptosis 1 and 2 are ubiquitin ligases for the apoptosis inducer Smac/DIABLO. J. Biol. Chem. 2003, 278, 10055–10060, doi:10.1074/jbc.M207197200.
[32]
Vucic, D.; Franklin, M.C.; Wallweber, H.J.; Das, K.; Eckelman, B.P.; Shin, H.; Elliott, L.O.; Kadkhodayan, S.; Deshayes, K.; Salvesen, G.S.; et al. Engineering ML-IAP to produce an extraordinarily potent caspase 9 inhibitor: implications for Smac-dependent anti-apoptotic activity of ML-IAP. Biochem. J. 2005, 385, 11–20, doi:10.1042/BJ20041108.
[33]
Wu, G.; Chai, J.; Suber, T.L.; Wu, J.W.; Du, C.; Wang, X.; Shi, Y. Structural basis of IAP recognition by Smac/DIABLO. Nature 2000, 408, 1008–1012.
[34]
Liu, Z.; Sun, C.; Olejniczak, E.T.; Meadows, R.P.; Betz, S.F.; Oost, T.; Herrmann, J.; Wu, J.C.; Fesik, S.W. Structural basis for binding of Smac/DIABLO to the XIAP BIR3 domain. Nature 2000, 408, 1004–1008, doi:10.1038/35050006.
[35]
Eckelman, B.P.; Salvesen, G.S.; Scott, F.L. Human inhibitor of apoptosis proteins: Why XIAP is the black sheep of the family. EMBO Rep. 2006, 7, 988–994, doi:10.1038/sj.embor.7400795.
[36]
Scott, F.L.; Denault, J.B.; Riedl, S.J.; Shin, H.; Renatus, M.; Salvesen, G.S. XIAP inhibits caspase-3 and -7 using two binding sites: evolutionarily conserved mechanism of IAPs. EMBO J. 2005, 24, 645–655, doi:10.1038/sj.emboj.7600544.
[37]
Shiozaki, E.N.; Chai, J.; Rigotti, D.J.; Riedl, S.J.; Li, P.; Srinivasula, S.M.; Alnemri, E.S.; Fairman, R.; Shi, Y. Mechanism of XIAP-mediated inhibition of caspase-9. Mol. Cell. 2003, 11, 519–527, doi:10.1016/S1097-2765(03)00054-6.
[38]
Riedl, S.J.; Renatus, M.; Schwarzenbacher, R.; Zhou, Q.; Sun, C.; Fesik, S.W.; Liddington, R.C.; Salvesen, G.S. Structural basis for the inhibition of caspase-3 by XIAP. Cell 2001, 104, 791–800, doi:10.1016/S0092-8674(01)00274-4.
[39]
Suzuki, Y.; Nakabayashi, Y.; Takahashi, R. 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. USA 2001, 98, 8662–8667.
[40]
Morizane, Y.; Honda, R.; Fukami, K.; Yasuda, H. X-linked inhibitor of apoptosis functions as ubiquitin ligase toward mature caspase-9 and cytosolic Smac/DIABLO. J. Biochem. 2005, 137, 125–132, doi:10.1093/jb/mvi029.
[41]
Broemer, M.; Tenev, T.; Rigbolt, K.T.; Hempel, S.; Blagoev, B.; Silke, J.; Ditzel, M.; Meier, P. Systematic in vivo RNAi analysis identifies IAPs as NEDD8-E3 ligases. Mol. Cell 2010, 40, 810–822, doi:10.1016/j.molcel.2010.11.011.
[42]
Schile, A.J.; Garcia-Fernandez, M.; Steller, H. Regulation of apoptosis by XIAP ubiquitin-ligase activity. Genes Dev. 2008, 22, 2256–2266, doi:10.1101/gad.1663108.
Wright, K.M.; Linhoff, M.W.; Potts, P.R.; Deshmukh, M. Decreased apoptosome activity with neuronal differentiation sets the threshold for strict IAP regulation of apoptosis. J. Cell. Biol. 2004, 167, 303–313, doi:10.1083/jcb.200406073.
[45]
Potts, M.B.; Vaughn, A.E.; McDonough, H.; Patterson, C.; Deshmukh, M. Reduced Apaf-1 levels in cardiomyocytes engage strict regulation of apoptosis by endogenous XIAP. J. Cell. Biol. 2005, 171, 925–930, doi:10.1083/jcb.200504082.
[46]
Choi, Y.E.; Butterworth, M.; Malladi, S.; Duckett, C.S.; Cohen, G.M.; Bratton, S.B. The E3 ubiquitin ligase cIAP1 binds and ubiquitinates caspase-3 and -7 via unique mechanisms at distinct steps in their processing. J. Biol. Chem. 2009, 284, 12772–12782.
[47]
Huang, H.; Joazeiro, C.A.; Bonfoco, E.; Kamada, S.; Leverson, J.D.; Hunter, T. The inhibitor of apoptosis, cIAP2, functions as a ubiquitin-protein ligase and promotes in vitro monoubiquitination of caspases 3 and 7. J. Biol. Chem. 2000, 275, 26661–26664.
[48]
Lee, T.V.; Fan, Y.; Wang, S.; Srivastava, M.; Broemer, M.; Meier, P.; Bergmann, A. Drosophila IAP1-mediated ubiquitylation controls activation of the initiator caspase DRONC independent of protein degradation. PLoS Genet. 2011, 7, e1002261, doi:10.1371/journal.pgen.1002261.
[49]
Davoodi, J.; Ghahremani, M.H.; Es-Haghi, A.; Mohammad-Gholi, A.; Mackenzie, A. Neuronal apoptosis inhibitory protein, NAIP, is an inhibitor of procaspase-9. Int. J. Biochem. Cell. Biol. 2010, 42, 958–964, doi:10.1016/j.biocel.2010.02.008.
Dueber, E.C.; Schoeffler, A.J.; Lingel, A.; Elliott, J.M.; Fedorova, A.V.; Giannetti, A.M.; Zobel, K.; Maurer, B.; Varfolomeev, E.; Wu, P.; et al. Antagonists induce a conformational change in cIAP1 that promotes autoubiquitination. Science 2011, 334, 376–380.
[52]
Vince, J.E.; Wong, W.W.; Khan, N.; Feltham, R.; Chau, D.; Ahmed, A.U.; Benetatos, C.A.; Chunduru, S.K.; Condon, S.M.; McKinlay, M.; et al. IAP Antagonists Target cIAP1 to Induce TNFalpha-Dependent Apoptosis. Cell 2007, 131, 682–693, doi:10.1016/j.cell.2007.10.037.
[53]
Varfolomeev, E.; Goncharov, T.; Fedorova, A.V.; Dynek, J.N.; Zobel, K.; Deshayes, K.; Fairbrother, W.J.; Vucic, D. c-IAP1 and c-IAP2 are critical mediators of tumor necrosis factor alpha (TNFalpha)-induced NF-kappaB activation. J. Biol. Chem. 2008, 283, 24295–24299.
[54]
Vanlangenakker, N.; Vanden Berghe, T.; Bogaert, P.; Laukens, B.; Zobel, K.; Deshayes, K.; Vucic, D.; Fulda, S.; Vandenabeele, P.; Bertrand, M.J. cIAP1 and TAK1 protect cells from TNF-induced necrosis by preventing RIP1/RIP3-dependent reactive oxygen species production. Cell. Death Differ. 2011, 18, 656–665, doi:10.1038/cdd.2010.138.
[55]
Petersen, S.L.; Wang, L.; Yalcin-Chin, A.; Li, L.; Peyton, M.; Minna, J.; Harran, P.; Wang, X. Autocrine TNFalpha signaling renders human cancer cells susceptible to Smac-mimetic-induced apoptosis. Cancer Cell. 2007, 12, 445–456, doi:10.1016/j.ccr.2007.08.029.
[56]
Gaither, A.; Porter, D.; Yao, Y.; Borawski, J.; Yang, G.; Donovan, J.; Sage, D.; Slisz, J.; Tran, M.; Straub, C.; et al. A Smac mimetic rescue screen reveals roles for inhibitor of apoptosis proteins in tumor necrosis factor-alpha signaling. Cancer Res. 2007, 67, 11493–11498.
[57]
Vince, J.E.; Chau, D.; Callus, B.; Wong, W.W.; Hawkins, C.J.; Schneider, P.; McKinlay, M.; Benetatos, C.A.; Condon, S.M.; Chunduru, S.K.; et al. TWEAK-FN14 signaling induces lysosomal degradation of a cIAP1-TRAF2 complex to sensitize tumor cells to TNFalpha. J. Cell. Biol. 2008, 182, 171–184, doi:10.1083/jcb.200801010.
[58]
Bertrand, M.J.; Milutinovic, S.; Dickson, K.M.; Ho, W.C.; Boudreault, A.; Durkin, J.; Gillard, J.W.; Jaquith, J.B.; Morris, S.J.; Barker, P.A. cIAP1 and cIAP2 facilitate cancer cell survival by functioning as E3 ligases that promote RIP1 ubiquitination. Mol. Cell. 2008, 30, 689–700, doi:10.1016/j.molcel.2008.05.014.
[59]
Park, S.M.; Yoon, J.B.; Lee, T.H. Receptor interacting protein is ubiquitinated by cellular inhibitor of apoptosis proteins (c-IAP1 and c-IAP2) in vitro. FEBS Lett. 2004, 566, 151–156, doi:10.1016/j.febslet.2004.04.021.
[60]
Geserick, P.; Hupe, M.; Moulin, M.; Wong, W.W.; Feoktistova, M.; Kellert, B.; Gollnick, H.; Silke, J.; Leverkus, M. Cellular IAPs inhibit a cryptic CD95-induced cell death by limiting RIP1 kinase recruitment. J. Cell. Biol. 2009, 187, 1037–1054, doi:10.1083/jcb.200904158.
[61]
Bertrand, M.J.; Lippens, S.; Staes, A.; Gilbert, B.; Roelandt, R.; De Medts, J.; Gevaert, K.; Declercq, W.; Vandenabeele, P. cIAP1/2 are direct E3 ligases conjugating diverse types of ubiquitin chains to receptor interacting proteins kinases 1 to 4 (RIP1–4). PLoS One 2011, 6, e22356.
[62]
Dynek, J.N.; Goncharov, T.; Dueber, E.C.; Fedorova, A.V.; Izrael-Tomasevic, A.; Phu, L.; Helgason, E.; Fairbrother, W.J.; Deshayes, K.; Kirkpatrick, D.S.; et al. c-IAP1 and UbcH5 promote K11-linked polyubiquitination of RIP1 in TNF signalling. EMBO J. 2010, 29, 4198–4209, doi:10.1038/emboj.2010.300.
[63]
Vandenabeele, P.; Galluzzi, L.; Vanden Berghe, T.; Kroemer, G. Molecular mechanisms of necroptosis: an ordered cellular explosion. Nat. Rev. Mol. Cell. Biol. 2010, 11, 700–714, doi:10.1038/nrm2970.
[64]
Moulin, M.; Anderton, H.; Voss, A.K.; Thomas, T.; Wong, W.W.; Bankovacki, A.; Feltham, R.; Chau, D.; Cook, W.D.; Silke, J.; et al. IAPs limit activation of RIP kinases by TNF receptor 1 during development. EMBO J. 2012, 31, 1679–1691, doi:10.1038/emboj.2012.18.
[65]
Hayden, M.S.; Ghosh, S. NF-kappaB, the first quarter-century: Remarkable progress and outstanding questions. Genes Dev. 2012, 26, 203–234, doi:10.1101/gad.183434.111.
[66]
Jin, H.S.; Lee, D.H.; Kim, D.H.; Chung, J.H.; Lee, S.J.; Lee, T.H. cIAP1, cIAP2, and XIAP act cooperatively via nonredundant pathways to regulate genotoxic stress-induced nuclear factor-kappaB activation. Cancer Res. 2009, 69, 1782–1791, doi:10.1158/0008-5472.CAN-08-2256.
[67]
Niu, J.; Shi, Y.; Iwai, K.; Wu, Z.H. LUBAC regulates NF-kappaB activation upon genotoxic stress by promoting linear ubiquitination of NEMO. EMBO J. 2011, 30, 3741–3753, doi:10.1038/emboj.2011.264.
Haas, T.L.; Emmerich, C.H.; Gerlach, B.; Schmukle, A.C.; Cordier, S.M.; Rieser, E.; Feltham, R.; Vince, J.; Warnken, U.; Wenger, T.; et al. Recruitment of the linear ubiquitin chain assembly complex stabilizes the TNF-R1 signaling complex and is required for TNF-mediated gene induction. Mol. Cell 2009, 36, 831–844, doi:10.1016/j.molcel.2009.10.013.
[70]
Lu, M.; Lin, S.C.; Huang, Y.; Kang, Y.J.; Rich, R.; Lo, Y.C.; Myszka, D.; Han, J.; Wu, H. XIAP induces NF-kappaB activation via the BIR1/TAB1 interaction and BIR1 dimerization. Mol. Cell 2007, 26, 689–702, doi:10.1016/j.molcel.2007.05.006.
[71]
Hinz, M.; Stilmann, M.; Arslan, S.C.; Khanna, K.K.; Dittmar, G.; Scheidereit, C. A cytoplasmic ATM-TRAF6-cIAP1 module links nuclear DNA damage signaling to ubiquitin-mediated NF-kappaB activation. Mol. Cell. 2010, 40, 63–74, doi:10.1016/j.molcel.2010.09.008.
[72]
Zarnegar, B.J.; Wang, Y.; Mahoney, D.J.; Dempsey, P.W.; Cheung, H.H.; He, J.; Shiba, T.; Yang, X.; Yeh, W.C.; Mak, T.W.; et al. Noncanonical NF-kappaB activation requires coordinated assembly of a regulatory complex of the adaptors cIAP1, cIAP2, TRAF2 and TRAF3 and the kinase NIK. Nat. Immunol. 2008, 9, 1371–1378, doi:10.1038/ni.1676.
[73]
Vallabhapurapu, S.; Matsuzawa, A.; Zhang, W.; Tseng, P.H.; Keats, J.J.; Wang, H.; Vignali, D.A.; Bergsagel, P.L.; Karin, M. Nonredundant and complementary functions of TRAF2 and TRAF3 in a ubiquitination cascade that activates NIK-dependent alternative NF-kappaB signaling. Nat. Immunol. 2008, 9, 1364–1370, doi:10.1038/ni.1678.
[74]
van der Waal, M.S.; Hengeveld, R.C.; van der Horst, A.; Lens, S.M. Cell division control by the Chromosomal Passenger Complex. Exp. Cell. Res. 2012, 318, 1407–1420, doi:10.1016/j.yexcr.2012.03.015.
[75]
Cartier, J.; Berthelet, J.; Marivin, A.; Gemble, S.; Edmond, V.; Plenchette, S.; Lagrange, B.; Hammann, A.; Dupoux, A.; Delva, L.; et al. Cellular inhibitor of apoptosis protein-1 (cIAP1) can regulate E2F1 transcription factor-mediated control of cyclin transcription. J. Biol. Chem. 2011, 286, 26406–26417.
[76]
Plenchette, S.; Cathelin, S.; Rebe, C.; Launay, S.; Ladoire, S.; Sordet, O.; Ponnelle, T.; Debili, N.; Phan, T.H.; Padua, R.A.; et al. Translocation of the inhibitor of apoptosis protein c-IAP1 from the nucleus to the Golgi in hematopoietic cells undergoing differentiation: A nuclear export signal-mediated event. Blood 2004, 104, 2035–2043, doi:10.1182/blood-2004-01-0065.
[77]
Didelot, C.; Lanneau, D.; Brunet, M.; Bouchot, A.; Cartier, J.; Jacquel, A.; Ducoroy, P.; Cathelin, S.; Decologne, N.; Chiosis, G.; et al. Interaction of heat-shock protein 90 beta isoform (HSP90 beta) with cellular inhibitor of apoptosis 1 (c-IAP1) is required for cell differentiation. Cell. Death Differ. 2008, 15, 859–866, doi:10.1038/cdd.2008.5.
[78]
Luscher, B.; Vervoorts, J. Regulation of gene transcription by the oncoprotein MYC. Gene 2012, 494, 145–160, doi:10.1016/j.gene.2011.12.027.
[79]
Xu, L.; Zhu, J.; Hu, X.; Zhu, H.; Kim, H.T.; LaBaer, J.; Goldberg, A.; Yuan, J. c-IAP1 cooperates with Myc by acting as a ubiquitin ligase for Mad1. Mol. Cell 2007, 28, 914–922, doi:10.1016/j.molcel.2007.10.027.
[80]
Holcik, M.; Yeh, C.; Korneluk, R.G.; Chow, T. Translational upregulation of X-linked inhibitor of apoptosis (XIAP) increases resistance to radiation induced cell death. Oncogene 2000, 19, 4174–4177, doi:10.1038/sj.onc.1203765.
[81]
Gu, L.; Zhu, N.; Zhang, H.; Durden, D.L.; Feng, Y.; Zhou, M. Regulation of XIAP translation and induction by MDM2 following irradiation. Cancer Cell. 2009, 15, 363–375, doi:10.1016/j.ccr.2009.03.002.
[82]
Nevins, T.A.; Harder, Z.M.; Korneluk, R.G.; Holcík, M. Distinct regulation of internal ribosome entry site-mediated translation following cellular stress is mediated by apoptotic fragments of eIF4G translation initiation factor family members eIF4GI and p97/DAP5/NAT1. J. Biol. Chem. 2003, 278, 3572–3579.
[83]
Hetz, C. The unfolded protein response: Controlling cell fate decisions under ER stress and beyond. Nat. Rev. Mol. Cell. Biol. 2012, 13, 89–102.
[84]
Hamanaka, R.B.; Bobrovnikova-Marjon, E.; Ji, X.; Liebhaber, S.A.; Diehl, J.A. PERK-dependent regulation of IAP translation during ER stress. Oncogene 2009, 28, 910–920, doi:10.1038/onc.2008.428.
[85]
Hu, P.; Han, Z.; Couvillon, A.D.; Exton, J.H. Critical role of endogenous Akt/IAPs and MEK1/ERK pathways in counteracting endoplasmic reticulum stress-induced cell death. J. Biol. Chem. 2004, 279, 49420–49429.
[86]
Hegde, R.; Srinivasula, S.M.; Datta, P.; Madesh, M.; Wassell, R.; Zhang, Z.; Cheong, N.; Nejmeh, J.; Fernandes-Alnemri, T.; Hoshino, S.; et al. The polypeptide chain-releasing factor GSPT1/eRF3 is proteolytically processed into an IAP-binding protein. J. Biol. Chem. 2003, 278, 38699–38706.
[87]
Nakamura, T.; Cho, D.H.; Lipton, S.A. Redox regulation of protein misfolding, mitochondrial dysfunction, synaptic damage, and cell death in neurodegenerative diseases. Exp. Neurol. 2012, 238, 12–21, doi:10.1016/j.expneurol.2012.06.032.
[88]
Russell, J.C.; Whiting, H.; Szuflita, N.; Hossain, M.A. Nuclear translocation of X-linked inhibitor of apoptosis (XIAP) determines cell fate after hypoxia ischemia in neonatal brain. J. Neurochem. 2008, 106, 1357–1370, doi:10.1111/j.1471-4159.2008.05482.x.
[89]
West, T.; Stump, M.; Lodygensky, G.; Neil, J.J.; Deshmukh, M.; Holtzman, D.M. Lack of X-linked inhibitor of apoptosis protein leads to increased apoptosis and tissue loss following neonatal brain injury. ASN Neuro 2009, 1, 43–53.
[90]
Hill, C.A.; Fitch, R.H. Sex differences in mechanisms and outcome of neonatal hypoxia-ischemia in rodent models: Implications for sex-specific neuroprotection in clinical neonatal practice. Neurol. Res. Int. 2012, 2012, 867531–867539.
[91]
Guegan, C.; Braudeau, J.; Couriaud, C.; Dietz, G.P.; Lacombe, P.; Bahr, M.; Nosten-Bertrand, M.; Onteniente, B. PTD-XIAP protects against cerebral ischemia by anti-apoptotic and transcriptional regulatory mechanisms. Neurobiol. Dis. 2006, 22, 177–186, doi:10.1016/j.nbd.2005.10.014.
[92]
Li, T.; Fan, Y.; Luo, Y.; Xiao, B.; Lu, C. In vivo delivery of a XIAP (BIR3-RING) fusion protein containing the protein transduction domain protects against neuronal death induced by seizures. Exp. Neurol. 2006, 197, 301–308, doi:10.1016/j.expneurol.2005.08.021.
Zhu, C.; Xu, F.; Fukuda, A.; Wang, X.; Fukuda, H.; Korhonen, L.; Hagberg, H.; Lannering, B.; Nilsson, M.; Eriksson, P.S.; et al. X chromosome-linked inhibitor of apoptosis protein reduces oxidative stress after cerebral irradiation or hypoxia-ischemia through up-regulation of mitochondrial antioxidants. Eur. J. Neurosci. 2007, 26, 3402–3410, doi:10.1111/j.1460-9568.2007.05948.x.
[95]
Kairisalo, M.; Korhonen, L.; Blomgren, K.; Lindholm, D. X-linked inhibitor of apoptosis protein increases mitochondrial antioxidants through NF-kappaB activation. Biochem. Biophys. Res. Commun. 2007, 364, 138–144, doi:10.1016/j.bbrc.2007.09.115.
[96]
Resch, U.; Schichl, Y.M.; Sattler, S.; de Martin, R. XIAP regulates intracellular ROS by enhancing antioxidant gene expression. Biochem. Biophys. Res. Commun. 2008, 375, 156–161, doi:10.1016/j.bbrc.2008.07.142.
[97]
Maine, G.N.; Mao, X.; Muller, P.A.; Komarck, C.M.; Klomp, L.W.; Burstein, E. COMMD1 expression is controlled by critical residues that determine XIAP binding. Biochem. J. 2009, 417, 601–609, doi:10.1042/BJ20080854.
[98]
Burstein, E.; Ganesh, L.; Dick, R.D.; van De Sluis, B.; Wilkinson, J.C.; Klomp, L.W.; Wijmenga, C.; Brewer, G.J.; Nabel, G.J.; Duckett, C.S. A novel role for XIAP in copper homeostasis through regulation of MURR1. EMBO J. 2004, 23, 244–254, doi:10.1038/sj.emboj.7600031.
Mufti, A.R.; Burstein, E.; Csomos, R.A.; Graf, P.C.; Wilkinson, J.C.; Dick, R.D.; Challa, M.; Son, J.K.; Bratton, S.B.; Su, G.L.; et al. XIAP Is a copper binding protein deregulated in Wilson's disease and other copper toxicosis disorders. Mol. Cell 2006, 21, 775–785, doi:10.1016/j.molcel.2006.01.033.
[101]
Holcik, M.; Thompson, C.S.; Yaraghi, Z.; Lefebvre, C.A.; MacKenzie, A.E.; Korneluk, R.G. The hippocampal neurons of neuronal apoptosis inhibitory protein 1 (NAIP1)-deleted mice display increased vulnerability to kainic acid-induced injury. Proc. Natl. Acad. Sci. USA 2000, 97, 2286–2290.
[102]
Masumu, M.; Hata, R. Recent advances in adenovirus-mediated gene therapy for cerebral ischemia. Curr. Gene Ther. 2003, 3, 43–48, doi:10.2174/1566523033347516.
[103]
Lewis, S.M.; Holcik, M. IRES in distress: Translational regulation of the inhibitor of apoptosis proteins XIAP and HIAP2 during cell stress. Cell. Death Differ. 2005, 12, 547–553, doi:10.1038/sj.cdd.4401602.
[104]
Parihar, A.; Eubank, T.D.; Doseff, A.I. Monocytes and macrophages regulate immunity through dynamic networks of survival and cell death. J. Innate Immun. 2010, 2, 204–215, doi:10.1159/000296507.
[105]
Lin, H.; Chen, C.; Chen, B.D. Resistance of bone marrow-derived macrophages to apoptosis is associated with the expression of X-linked inhibitor of apoptosis protein in primary cultures of bone marrow cells. Biochem. J. 2001, 353, 299–306, doi:10.1042/0264-6021:3530299.
[106]
Miranda, M.B.; Dyer, K.F.; Grandis, J.R.; Johnson, D.E. Differential activation of apoptosis regulatory pathways during monocytic vs granulocytic differentiation: A requirement for Bcl-X(L)and XIAP in the prolonged survival of monocytic cells. Leukemia 2003, 17, 390–400, doi:10.1038/sj.leu.2402779.
[107]
Hida, A.; Kawakami, A.; Nakashima, T.; Yamasaki, S.; Sakai, H.; Urayama, S.; Ida, H.; Nakamura, H.; Migita, K.; Kawabe, Y.; et al. Nuclear factor-kappaB and caspases co-operatively regulate the activation and apoptosis of human macrophages. Immunology 2000, 99, 553–560, doi:10.1046/j.1365-2567.2000.00985.x.
[108]
Lin, H.; Chen, C.; Li, X.; Chen, B.D. Activation of the MEK/MAPK pathway is involved in bryostatin1-induced monocytic differenciation and up-regulation of X-linked inhibitor of apoptosis protein. Exp. Cell. Res. 2002, 272, 192–198, doi:10.1006/excr.2001.5417.
[109]
Conte, D.; Holcik, M.; Lefebvre, C.A.; Lacasse, E.; Picketts, D.J.; Wright, K.E.; Korneluk, R.G. Inhibitor of apoptosis protein cIAP2 is essential for lipopolysaccharide-induced macrophage survival. Mol. Cell. Biol. 2006, 26, 699–708, doi:10.1128/MCB.26.2.699-708.2006.
[110]
Cui, X.; Imaizumi, T.; Yoshida, H.; Tanji, K.; Matsumiya, T.; Satoh, K. Lipopolysaccharide induces the expression of cellular inhibitor of apoptosis protein-2 in human macrophages. Biochim. Biophys. Acta 2000, 1524, 178–182, doi:10.1016/S0304-4165(00)00155-0.
[111]
Matsunaga, T.; Ishida, T.; Takekawa, M.; Nishimura, S.; Adachi, M.; Imai, K. Analysis of gene expression during maturation of immature dendritic cells derived from peripheral blood monocytes. Scand. J. Immunol. 2002, 56, 593–601, doi:10.1046/j.1365-3083.2002.01179.x.
[112]
Dupoux, A.; Cartier, J.; Cathelin, S.; Filomenko, R.; Solary, E.; Dubrez-Daloz, L. cIAP1-dependent TRAF2 degradation regulates the differentiation of monocytes into macrophages and their response to CD40 ligand. Blood 2009, 113, 175–185, doi:10.1182/blood-2008-02-137919.
[113]
Busca, A.; Saxena, M.; Kumar, A. Critical role for antiapoptotic Bcl-xL and Mcl-1 in human macrophage survival and cellular IAP1/2 (cIAP1/2) in resistance to HIV-Vpr-induced apoptosis. J. Biol. Chem. 2012, 287, 15118–15133.
[114]
Zender, L.; Spector, M.S.; Xue, W.; Flemming, P.; Cordon-Cardo, C.; Silke, J.; Fan, S.T.; Luk, J.M.; Wigler, M.; Hannon, G.J.; et al. Identification and validation of oncogenes in liver cancer using an integrative oncogenomic approach. Cell 2006, 125, 1253–1267, doi:10.1016/j.cell.2006.05.030.
[115]
Ma, O.; Cai, W.W.; Zender, L.; Dayaram, T.; Shen, J.; Herron, A.J.; Lowe, S.W.; Man, T.K.; Lau, C.C.; Donehower, L.A. MMP13, Birc2 (cIAP1), and Birc3 (cIAP2), amplified on chromosome 9, collaborate with p53 deficiency in mouse osteosarcoma progression. Cancer Res. 2009, 69, 2559–2567.
[116]
Cheng, L.; Zhou, Z.; Flesken-Nikitin, A.; Toshkov, I.A.; Wang, W.; Camps, J.; Ried, T.; Nikitin, A.Y. Rb inactivation accelerates neoplastic growth and substitutes for recurrent amplification of cIAP1, cIAP2 and Yap1 in sporadic mammary carcinoma associated with p53 deficiency. Oncogene 2010, 29, 5700–5711, doi:10.1038/onc.2010.300.
[117]
Imoto, I.; Tsuda, H.; Hirasawa, A.; Miura, M.; Sakamoto, M.; Hirohashi, S.; Inazawa, J. Expression of cIAP1, a target for 11q22 amplification, correlates with resistance of cervical cancers to radiotherapy. Cancer Res. 2002, 62, 4860–4866.
[118]
Dai, Z.; Zhu, W.G.; Morrison, C.D.; Brena, R.M.; Smiraglia, D.J.; Raval, A.; Wu, Y.Z.; Rush, L.J.; Ross, P.; Molina, J.R.; et al. A comprehensive search for DNA amplification in lung cancer identifies inhibitors of apoptosis cIAP1 and cIAP2 as candidate oncogenes. Hum. Mol. Genet. 2003, 12, 791–801, doi:10.1093/hmg/ddg083.
Imoto, I.; Yang, Z.Q.; Pimkhaokham, A.; Tsuda, H.; Shimada, Y.; Imamura, M.; Ohki, M.; Inazawa, J. Identification of cIAP1 as a candidate target gene within an amplicon at 11q22 in esophageal squamous cell carcinomas. Cancer Res. 2001, 61, 6629–6634.
[121]
Varfolomeev, E.; Wayson, S.M.; Dixit, V.M.; Fairbrother, W.J.; Vucic, D. The inhibitor of apoptosis protein fusion c-IAP2.MALT1 stimulates NF-kappaB activation independently of TRAF1 AND TRAF2. J. Biol. Chem. 2006, 281, 29022–29029.
[122]
Garrison, J.B.; Samuel, T.; Reed, J.C. TRAF2-binding BIR1 domain of c-IAP2/MALT1 fusion protein is essential for activation of NF-kappaB. Oncogene 2009, 28, 1584–1593, doi:10.1038/onc.2009.17.
[123]
Oberoi, T.K.; Dogan, T.; Hocking, J.C.; Scholz, R.P.; Mooz, J.; Anderson, C.L.; Karreman, C.; Meyer Zu Heringdorf, D.; Schmidt, G.; Ruonala, M.; et al. IAPs regulate the plasticity of cell migration by directly targeting Rac1 for degradation. Embo J. 2011, 31, 14–28, doi:10.1038/emboj.2011.423.
[124]
Dogan, T.; Harms, G.S.; Hekman, M.; Karreman, C.; Oberoi, T.K.; Alnemri, E.S.; Rapp, U.R.; Rajalingam, K. X-linked and cellular IAPs modulate the stability of C-RAF kinase and cell motility. Nat. Cell. Biol. 2008, 10, 1447–1455, doi:10.1038/ncb1804.
[125]
Keats, J.J.; Fonseca, R.; Chesi, M.; Schop, R.; Baker, A.; Chng, W.J.; Van Wier, S.; Tiedemann, R.; Shi, C.X.; Sebag, M.; et al. Promiscuous mutations activate the noncanonical NF-kappaB pathway in multiple myeloma. Cancer Cell. 2007, 12, 131–144, doi:10.1016/j.ccr.2007.07.003.
[126]
Annunziata, C.M.; Davis, R.E.; Demchenko, Y.; Bellamy, W.; Gabrea, A.; Zhan, F.; Lenz, G.; Hanamura, I.; Wright, G.; Xiao, W.; et al. Frequent engagement of the classical and alternative NF-kappaB pathways by diverse genetic abnormalities in multiple myeloma. Cancer Cell. 2007, 12, 115–130, doi:10.1016/j.ccr.2007.07.004.
Tsang, A.H.; Lee, Y.I.; Ko, H.S.; Savitt, J.M.; Pletnikova, O.; Troncoso, J.C.; Dawson, V.L.; Dawson, T.M.; Chung, K.K. S-nitrosylation of XIAP compromises neuronal survival in Parkinson's disease. Proc. Natl. Acad. Sci. USA 2009, 106, 4900–4905.
[129]
Goffredo, D.; Rigamonti, D.; Zuccato, C.; Tartari, M.; Valenza, M.; Cattaneo, E. Prevention of cytosolic IAPs degradation: A potential pharmacological target in Huntington's Disease. Pharmacol. Res. 2005, 52, 140–150, doi:10.1016/j.phrs.2005.01.006.
[130]
Watihayati, M.S.; Fatemeh, H.; Marini, M.; Atif, A.B.; Zahiruddin, W.M.; Sasongko, T.H.; Tang, T.H.; Zabidi-Hussin, Z.A.; Nishio, H.; Zilfalil, B.A. Combination of SMN2 copy number and NAIP deletion predicts disease severity in spinal muscular atrophy. Brain Dev. 2009, 31, 42–45, doi:10.1016/j.braindev.2008.08.012.
[131]
Weiss, K.H.; Runz, H.; Noe, B.; Gotthardt, D.N.; Merle, U.; Ferenci, P.; Stremmel, W.; Fullekrug, J. Genetic analysis of BIRC4/XIAP as a putative modifier gene of Wilson disease. J. Inherit. Metab. Dis. 2010, 10, 1007–1014.
