Gene Symbol: c-IAP1
Description: baculoviral IAP repeat containing 2
Alias: API1, HIAP2, Hiap-2, MIHB, RNF48, c-IAP1, cIAP1, baculoviral IAP repeat-containing protein 2, IAP homolog B, IAP-2, NFR2-TRAF signalling complex protein, RING finger protein 48, RING-type E3 ubiquitin transferase BIRC2, TNFR2-TRAF-signaling complex protein 2, apoptosis inhibitor 1, cellular inhibitor of apoptosis 1, inhibitor of apoptosis protein 2
Species: human
Products:     c-IAP1

Top Publications

  1. Bertrand M, Milutinovic S, Dickson K, Ho W, Boudreault A, Durkin J, et al. cIAP1 and cIAP2 facilitate cancer cell survival by functioning as E3 ligases that promote RIP1 ubiquitination. Mol Cell. 2008;30:689-700 pubmed publisher
    ..In this report, we show that cIAP1 and cIAP2 promote cancer cell survival by functioning as E3 ubiquitin ligases that maintain constitutive ..
  2. Yang Y, Fang S, Jensen J, Weissman A, Ashwell J. Ubiquitin protein ligase activity of IAPs and their degradation in proteasomes in response to apoptotic stimuli. Science. 2000;288:874-7 pubmed
    ..Autoubiquitination and degradation of IAPs may be a key event in the apoptotic program. ..
  3. Clem R, Sheu T, Richter B, He W, Thornberry N, Duckett C, et al. c-IAP1 is cleaved by caspases to produce a proapoptotic C-terminal fragment. J Biol Chem. 2001;276:7602-8 pubmed
    ..To the contrary, deletion of the caspase recruitment domain increased proapoptotic activity, apparently by stabilizing the C-terminal fragment. ..
  4. Varfolomeev E, Wayson S, Dixit V, Fairbrother W, Vucic D. The inhibitor of apoptosis protein fusion c-IAP2.MALT1 stimulates NF-kappaB activation independently of TRAF1 AND TRAF2. J Biol Chem. 2006;281:29022-9 pubmed
    ..Therefore, the t(11, 18)(q21;q21) translocation creating the c-IAP2.MALT1 fusion protein activates NF-kappaB and contributes to human malignancy in the absence of signaling adaptors that might otherwise regulate its activity. ..
  5. Cartier J, Berthelet J, Marivin A, Gemble S, Edmond V, Plenchette S, et al. Cellular inhibitor of apoptosis protein-1 (cIAP1) can regulate E2F1 transcription factor-mediated control of cyclin transcription. J Biol Chem. 2011;286:26406-17 pubmed publisher
    The inhibitor of apoptosis protein cIAP1 (cellular inhibitor of apoptosis protein-1) is a potent regulator of the tumor necrosis factor (TNF) receptor family and NF-?B signaling pathways in the cytoplasm...
  6. Komander D, Reyes Turcu F, Licchesi J, Odenwaelder P, Wilkinson K, Barford D. Molecular discrimination of structurally equivalent Lys 63-linked and linear polyubiquitin chains. EMBO Rep. 2009;10:466-73 pubmed publisher
    ..Our results highlight remarkable specificity determinants within the ubiquitin system. ..
  7. Sanjo H, Zajonc D, Braden R, Norris P, Ware C. Allosteric regulation of the ubiquitin:NIK and ubiquitin:TRAF3 E3 ligases by the lymphotoxin-beta receptor. J Biol Chem. 2010;285:17148-55 pubmed publisher
    ..These results indicate the LTbetaR modifies the ubiquitin:NIK E3 ligase, and also acts as an allosteric regulator of the ubiquitin:TRAF E3 ligase. ..
  8. Varfolomeev E, Blankenship J, Wayson S, Fedorova A, Kayagaki N, Garg P, et al. IAP antagonists induce autoubiquitination of c-IAPs, NF-kappaB activation, and TNFalpha-dependent apoptosis. Cell. 2007;131:669-81 pubmed
    ..Through their ubiquitin E3 ligase activities c-IAP1 and c-IAP2 promote proteasomal degradation of NIK, the central ser/thr kinase in the noncanonical NF-kappaB pathway. ..
  9. Blankenship J, Varfolomeev E, Goncharov T, Fedorova A, Kirkpatrick D, Izrael Tomasevic A, et al. Ubiquitin binding modulates IAP antagonist-stimulated proteasomal degradation of c-IAP1 and c-IAP2(1). Biochem J. 2009;417:149-60 pubmed publisher
    ..These results suggest that ubiquitin binding may be an important mechanism for rapid turnover of auto-ubiquitinated c-IAP1 and c-IAP2. ..

More Information


  1. Eckelman B, Salvesen G. The human anti-apoptotic proteins cIAP1 and cIAP2 bind but do not inhibit caspases. J Biol Chem. 2006;281:3254-60 pubmed
    ..Consequently, although the binding function of the cIAP BIRs may be important for their physiologic function, caspase inhibition is not. ..
  2. Darding M, Feltham R, Tenev T, Bianchi K, Benetatos C, Silke J, et al. Molecular determinants of Smac mimetic induced degradation of cIAP1 and cIAP2. Cell Death Differ. 2011;18:1376-86 pubmed publisher
    The inhibitors of apoptosis (IAP) proteins cIAP1 and cIAP2 have recently emerged as key ubiquitin-E3 ligases regulating innate immunity and cell survival...
  3. Qi Y, Xia P. Cellular inhibitor of apoptosis protein-1 (cIAP1) plays a critical role in ?-cell survival under endoplasmic reticulum stress: promoting ubiquitination and degradation of C/EBP homologous protein (CHOP). J Biol Chem. 2012;287:32236-45 pubmed publisher
    ..We report herein a critical role of cellular inhibitor of apoptosis protein-1 (cIAP1) in controlling ?-cell survival under ER stress...
  4. Dueber E, Schoeffler A, Lingel A, Elliott J, Fedorova A, Giannetti A, et al. Antagonists induce a conformational change in cIAP1 that promotes autoubiquitination. Science. 2011;334:376-80 pubmed publisher
    ..Here biochemical and structural studies reveal that the unliganded, multidomain cIAP1 sequesters the RING domain within a compact, monomeric structure that prevents RING dimerization...
  5. Micheau O, Tschopp J. Induction of TNF receptor I-mediated apoptosis via two sequential signaling complexes. Cell. 2003;114:181-90 pubmed
    ..Thus, TNFR1-mediated-signal transduction includes a checkpoint, resulting in cell death (via complex II) in instances where the initial signal (via complex I, NF-kappa B) fails to be activated. ..
  6. Mace P, Smits C, Vaux D, Silke J, Day C. Asymmetric recruitment of cIAPs by TRAF2. J Mol Biol. 2010;400:8-15 pubmed publisher
    ..In this study, we reconstituted the complex between baculoviral IAP repeat (BIR) 1 of cIAP1 and the coiled-coil region of TRAF2, solved the structure of BIR1 from cIAP1, and mapped key binding residues on ..
  7. Warnakulasuriyarachchi D, Cerquozzi S, Cheung 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;279:17148-57 pubmed
    ..Here we demonstrate that the expression of one member of the IAP family, HIAP2, is induced in response to ER stress and attenuates ER stress-induced cell death...
  8. Varfolomeev E, Goncharov T, Fedorova A, Dynek J, Zobel K, Deshayes K, et al. c-IAP1 and c-IAP2 are critical mediators of tumor necrosis factor alpha (TNFalpha)-induced NF-kappaB activation. J Biol Chem. 2008;283:24295-9 pubmed publisher
    ..Therefore, c-IAP1 and c-IAP2 are required for TNFalpha-stimulated RIP1 ubiquitination and NF-kappaB activation. ..
  9. Xu M, Skaug B, Zeng W, Chen Z. A ubiquitin replacement strategy in human cells reveals distinct mechanisms of IKK activation by TNFalpha and IL-1beta. Mol Cell. 2009;36:302-14 pubmed publisher
    ..We further show that IKK activation by TNFalpha requires Ubc5, which functions with the E3 cIAP1 to catalyze polyubiquitination of RIP1 not restricted to K63 of ubiquitin...
  10. Bertrand M, Doiron K, Labbe K, Korneluk R, Barker P, Saleh M. Cellular inhibitors of apoptosis cIAP1 and cIAP2 are required for innate immunity signaling by the pattern recognition receptors NOD1 and NOD2. Immunity. 2009;30:789-801 pubmed publisher
    ..Here, we report that cIAP1 and cIAP2 are E3 ubiquitin ligases that are required for receptor-interacting protein 2 (RIP2) ubiquitination and ..
  11. Hu S, Yang X. Cellular inhibitor of apoptosis 1 and 2 are ubiquitin ligases for the apoptosis inducer Smac/DIABLO. J Biol Chem. 2003;278:10055-60 pubmed
    ..Here we show that cIAP1 and cIAP2 are E3 ubiquitin-protein isopeptide ligases (ubiquitin ligases) for Smac...
  12. Gyrd Hansen M, Darding M, Miasari M, Santoro M, Zender L, Xue W, 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;10:1309-17 pubmed publisher
    ..We found that the UBA domain is essential for the oncogenic potential of cIAP1, to maintain endothelial cell survival and to protect cells from TNF-alpha-induced apoptosis...
  13. Arnt C, Chiorean M, Heldebrant M, Gores G, Kaufmann S. Synthetic Smac/DIABLO peptides enhance the effects of chemotherapeutic agents by binding XIAP and cIAP1 in situ. J Biol Chem. 2002;277:44236-43 pubmed
    ..analysis demonstrated that the Smac-penetratin fusion peptide crossed the cellular membrane, bound XIAP and cIAP1, displaced caspase-3 from cytoplasmic aggregates, and enhanced drug-induced caspase action in situ...
  14. Roy N, Deveraux Q, Takahashi R, Salvesen G, Reed J. The c-IAP-1 and c-IAP-2 proteins are direct inhibitors of specific caspases. EMBO J. 1997;16:6914-25 pubmed
    ..Taken together, these findings suggest that c-IAP-1 and c-IAP-2 function similarly to XIAP by inhibiting the distal cell death proteases, caspases-3 and -7, whereas NAIP presumably inhibits apoptosis via other targets. ..
  15. Jin H, Lee D, Kim D, Chung J, Lee S, Lee T. cIAP1, cIAP2, and XIAP act cooperatively via nonredundant pathways to regulate genotoxic stress-induced nuclear factor-kappaB activation. Cancer Res. 2009;69:1782-91 pubmed publisher
    ..We also show that cIAP1 mediates NEMO ubiquitination and cIAP2 regulates an event downstream of NEMO ubiquitination...
  16. Dynek J, Goncharov T, Dueber E, Fedorova A, Izrael Tomasevic A, Phu L, et al. c-IAP1 and UbcH5 promote K11-linked polyubiquitination of RIP1 in TNF signalling. EMBO J. 2010;29:4198-209 pubmed publisher
    ..Lastly, NF-?B essential modifier efficiently binds K11-linked ubiquitin chains, suggesting that this ubiquitin linkage may have a signalling role in the activation of proliferative cellular pathways. ..
  17. Feltham R, Bettjeman B, Budhidarmo R, Mace P, Shirley S, Condon S, et al. Smac mimetics activate the E3 ligase activity of cIAP1 protein by promoting RING domain dimerization. J Biol Chem. 2011;286:17015-28 pubmed publisher
    ..The cIAP1 and cIAP2 paralogs bear three N-terminal baculoviral IAP repeat (BIR) domains and a C-terminal E3 ligase RING ..
  18. Haas T, Emmerich C, Gerlach B, Schmukle A, Cordier S, Rieser E, 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;36:831-44 pubmed publisher
    ..chains of different linkage types and that its recruitment to the TNF-RSC is impaired in TRADD-, TRAF2-, and cIAP1/2- but not in RIP1- or NEMO-deficient MEFs...
  19. Csomos R, Brady G, Duckett C. Enhanced cytoprotective effects of the inhibitor of apoptosis protein cellular IAP1 through stabilization with TRAF2. J Biol Chem. 2009;284:20531-9 pubmed publisher
    ..Therefore, this study describes an intriguing cytoprotective mechanism utilized by c-IAP1 and provides critical insight into how IAP proteins function to alter the apoptotic threshold. ..
  20. Verhagen A, Ekert P, Pakusch M, Silke J, Connolly L, Reid G, et al. Identification of DIABLO, a mammalian protein that promotes apoptosis by binding to and antagonizing IAP proteins. Cell. 2000;102:43-53 pubmed
    ..DIABLO (direct IAP binding protein with low pI) is a novel protein that can bind MIHA and can also interact with MIHB and MIHC and the baculoviral IAP, OpIAP...
  21. Li X, Yang Y, Ashwell J. TNF-RII and c-IAP1 mediate ubiquitination and degradation of TRAF2. Nature. 2002;416:345-7 pubmed
    ..These findings identify a physiologic role for c-IAP1 and define a mechanism by which TNF-RII-regulated ubiquitin protein ligase activity can potentiate TNF-induced apoptosis. ..
  22. Samuel T, Welsh K, Lober T, Togo S, Zapata J, Reed J. Distinct BIR domains of cIAP1 mediate binding to and ubiquitination of tumor necrosis factor receptor-associated factor 2 and second mitochondrial activator of caspases. J Biol Chem. 2006;281:1080-90 pubmed
    ..Here, we compared the structural features of cIAP1 responsible for its interactions with two known target proteins, TRAF2 and SMAC...
  23. Wu C, Conze D, Li X, Ying S, Hanover J, Ashwell J. TNF-alpha induced c-IAP1/TRAF2 complex translocation to a Ubc6-containing compartment and TRAF2 ubiquitination. EMBO J. 2005;24:1886-98 pubmed
    ..Therefore, the ER plays a key role in the TNF-R-mediated signal transduction cascade by acting as a site of assembly for E2/E3/substrate complexes. ..
  24. Shibata Y, Oyama M, Kozuka Hata H, Han X, Tanaka Y, Gohda J, et al. p47 negatively regulates IKK activation by inducing the lysosomal degradation of polyubiquitinated NEMO. Nat Commun. 2012;3:1061 pubmed publisher
  25. Varfolomeev E, Goncharov T, Maecker H, Zobel K, Komuves L, Deshayes K, et al. Cellular inhibitors of apoptosis are global regulators of NF-?B and MAPK activation by members of the TNF family of receptors. Sci Signal. 2012;5:ra22 pubmed publisher
    ..These results define c-IAP proteins as critical regulators of the activation of NF-?B and MAPK signaling pathways by members of the TNFR superfamily. ..
  26. Che X, Yang D, Zong H, Wang J, Li X, Chen F, et al. Nuclear cIAP1 overexpression is a tumor stage- and grade-independent predictor of poor prognosis in human bladder cancer patients. Urol Oncol. 2012;30:450-6 pubmed publisher
    To evaluate the tumor-related expression profile of cellular inhibitor of apoptosis protein 1 (cIAP1) and cellular inhibitor of apoptosis protein (cIAP2) in patients with bladder cell carcinoma (BCC) and to investigate its potential ..
  27. Silke J, Kratina T, Chu D, Ekert P, Day C, Pakusch M, et al. Determination of cell survival by RING-mediated regulation of inhibitor of apoptosis (IAP) protein abundance. Proc Natl Acad Sci U S A. 2005;102:16182-7 pubmed
    ..Here we show that the RING domain of cIAP1 allows it to bind directly to the RING of X-linked IAP, causing its ubiquitylation and degradation by the ..
  28. Kuai J, Nickbarg E, Wooters J, Qiu Y, Wang J, Lin L. Endogenous association of TRAF2, TRAF3, cIAP1, and Smac with lymphotoxin beta receptor reveals a novel mechanism of apoptosis. J Biol Chem. 2003;278:14363-9 pubmed
    ..Four of five proteins identified, TRAF2, TRAF3, cIAP1, and Smac, are reported here...
  29. Guicciardi M, Mott J, Bronk S, Kurita S, Fingas C, Gores G. Cellular inhibitor of apoptosis 1 (cIAP-1) degradation by caspase 8 during TNF-related apoptosis-inducing ligand (TRAIL)-induced apoptosis. Exp Cell Res. 2011;317:107-16 pubmed publisher
    ..Targeted depletion of cIAP-1 by SMAC mimetics in conjunction with TRAIL may be beneficial for the treatment of human hepatobiliary malignancies. ..
  30. Gyrd Hansen M, Meier P. IAPs: from caspase inhibitors to modulators of NF-kappaB, inflammation and cancer. Nat Rev Cancer. 2010;10:561-74 pubmed publisher
    ..Recent studies indicate that IAPs not only regulate caspases and apoptosis, but also modulate inflammatory signalling and immunity, mitogenic kinase signalling, proliferation and mitosis, as well as cell invasion and metastasis. ..
  31. Dohi T, Okada K, Xia F, Wilford C, Samuel T, Welsh K, et al. An IAP-IAP complex inhibits apoptosis. J Biol Chem. 2004;279:34087-90 pubmed
    ..Therefore, orchestration of an IAP-IAP complex regulates apoptosis. ..
  32. Yang Q, Du C. Smac/DIABLO selectively reduces the levels of c-IAP1 and c-IAP2 but not that of XIAP and livin in HeLa cells. J Biol Chem. 2004;279:16963-70 pubmed
    ..Taken together, Smac may serve as a key molecule in vivo to selectively reduce the protein level of c-IAPs through the ubiquitin/proteasome pathway. ..
  33. Vince J, Wong W, Khan N, Feltham R, Chau D, Ahmed A, et al. IAP antagonists target cIAP1 to induce TNFalpha-dependent apoptosis. Cell. 2007;131:682-93 pubmed
    ..is blocked by the caspase 8 inhibitor crmA and that IAP antagonists activate NF-kappaB signaling via inhibtion of cIAP1. In sensitive tumor lines, IAP antagonist induced NF-kappaB-stimulated production of TNFalpha that killed cells in ..
  34. Tang E, Wang C, Xiong Y, Guan K. A role for NF-kappaB essential modifier/IkappaB kinase-gamma (NEMO/IKKgamma) ubiquitination in the activation of the IkappaB kinase complex by tumor necrosis factor-alpha. J Biol Chem. 2003;278:37297-305 pubmed
    ..Also, defective NEMO ubiquitination may be responsible for the impaired cellular NF-kappaB signaling found in patients with HED-ID. ..
  35. Vince J, Pantaki D, Feltham R, Mace P, Cordier S, Schmukle A, et al. TRAF2 must bind to cellular inhibitors of apoptosis for tumor necrosis factor (tnf) to efficiently activate nf-{kappa}b and to prevent tnf-induced apoptosis. J Biol Chem. 2009;284:35906-15 pubmed publisher
    Tumor necrosis factor (TNF) receptor-associated factor-2 (TRAF2) binds to cIAP1 and cIAP2 (cIAP1/2) and recruits them to the cytoplasmic domain of several members of the TNF receptor (TNFR) superfamily, including the TNF-TNFR1 ligand-..
  36. Chang Y, Cheng C, Chang L, Jong Y, Yuo C. The F-box protein Fbxo7 interacts with human inhibitor of apoptosis protein cIAP1 and promotes cIAP1 ubiquitination. Biochem Biophys Res Commun. 2006;342:1022-6 pubmed
    Human cIAP1 protein is a member of the inhibitor of apoptosis proteins (IAPs) that are involved in apoptosis regulation and an increasing number of other functions, including cell cycle and intracellular signal transduction...
  37. Rothe M, Pan M, Henzel W, Ayres T, Goeddel D. The TNFR2-TRAF signaling complex contains two novel proteins related to baculoviral inhibitor of apoptosis proteins. Cell. 1995;83:1243-52 pubmed
    ..The recruitment of c-IAP1 or c-IAP2 to the TNFR2 signaling complex requires a TRAF2-TRAF1 heterocomplex. ..
  38. Yin Q, Lamothe B, Darnay B, Wu H. Structural basis for the lack of E2 interaction in the RING domain of TRAF2. Biochemistry. 2009;48:10558-67 pubmed publisher
    ..Our structural observation should prompt a re-evaluation of the role of TRAF2 in TNFalpha signaling and may indicate that TRAF2-associated proteins such as cIAPs may be the ubiquitin ligases for NF-kappaB signaling. ..
  39. Ponnelle T, Chapusot C, Martin L, Bonithon Kopp C, Bouvier A, Plenchette S, et al. Subcellular expression of c-IAP1 and c-IAP2 in colorectal cancers: relationships with clinicopathological features and prognosis. Pathol Res Pract. 2003;199:723-31 pubmed
    ..These associations were not statistically significant, but this work underlines the importance of taking into account the subcellular location of the IAP family members in the evaluation of their prognostic significance. ..
  40. Borghi A, Haegman M, Fischer R, Carpentier I, Bertrand M, Libert C, et al. The E3 ubiquitin ligases HOIP and cIAP1 are recruited to the TNFR2 signaling complex and mediate TNFR2-induced canonical NF-κB signaling. Biochem Pharmacol. 2018;153:292-298 pubmed publisher
    ..Also cIAP1, a E3 ubiquitin ligase able to modify proteins with K63-polyubiquitin chains, was recruited to the TNFR2 signaling ..
  41. Xu L, Zhu J, Hu X, Zhu H, Kim H, Labaer J, et al. c-IAP1 cooperates with Myc by acting as a ubiquitin ligase for Mad1. Mol Cell. 2007;28:914-22 pubmed
    ..Our results demonstrate that c-IAP1 exerts its oncogenic functions by promoting the degradation of an important negative regulator in the Myc pathway. ..
  42. Choi J, Kim D, Park M, Um J, Han J, Park S, et al. AIMP2 promotes TNFalpha-dependent apoptosis via ubiquitin-mediated degradation of TRAF2. J Cell Sci. 2009;122:2710-5 pubmed publisher
    ..These findings suggest that AIMP2 can mediate the pro-apoptotic activity of TNFalpha via the downregulation of TRAF2 expression. ..
  43. Seo T, Lee J, Choi Y, Jeong D, Lee S, Yoo S. A novel function of cIAP1 as a mediator of CHIP-driven eIF4E regulation. Sci Rep. 2017;7:9816 pubmed publisher
    ..that eIF4E is efficiently regulated by dual mechanisms, both involving human inhibitor of apoptosis family protein cIAP1. cIAP1 itself ubiquitinates eIF4E as an E3 ligase, and interestingly, cIAP1 also functions as a mediator to ..
  44. Feoktistova M, Geserick P, Panayotova Dimitrova D, Leverkus M. Pick your poison: the Ripoptosome, a cell death platform regulating apoptosis and necroptosis. Cell Cycle. 2012;11:460-7 pubmed publisher
    ..Our study thus supports and extends the intriguing role of the Ripoptosome for the regulation of apoptosis and necroptosis. ..
  45. Akyurek N, Ren Y, Rassidakis G, Schlette E, Medeiros L. Expression of inhibitor of apoptosis proteins in B-cell non-Hodgkin and Hodgkin lymphomas. Cancer. 2006;107:1844-51 pubmed
    ..Eight IAPs have been identified in humans, of which cIAP1, cIAP2, and XIAP are well known. IAPs are being investigated as potential treatment targets in cancer patients...
  46. Tigno Aranjuez J, Bai X, Abbott D. A discrete ubiquitin-mediated network regulates the strength of NOD2 signaling. Mol Cell Biol. 2013;33:146-58 pubmed publisher
    ..Inhibitor-of-apoptosis (IAP) proteins, particularly cIAP1, are essential mediators of NOD2 signaling, and in this work, we describe a molecular mechanism for cIAP1's ..
  47. Jang H, Chung Y, Baik J, Choi Y, Park I, Jung Y, et al. Caspase-cleaved TRAF1 negatively regulates the antiapoptotic signals of TRAF2 during TNF-induced cell death. Biochem Biophys Res Commun. 2001;281:499-505 pubmed
    ..These results indicate that caspase-dependent cleavage of TRAF1 generates TRAF1-c fragments that are able to bind TRAF2, and then sequester TRAF2 from the TNF-R1 complex, rendering cells, at least in part, sensitive to TNF. ..
  48. Schliep S, Decker T, Schneller F, Wagner H, Hacker G. Functional evaluation of the role of inhibitor of apoptosis proteins in chronic lymphocytic leukemia. Exp Hematol. 2004;32:556-62 pubmed
    ..This is likely due to the high expression of Smac/DIABLO in CLL cells that is sufficient to overcome the caspase-inhibiting effect of IAP. ..
  49. Tomoshige S, Naito M, Hashimoto Y, Ishikawa M. Degradation of HaloTag-fused nuclear proteins using bestatin-HaloTag ligand hybrid molecules. Org Biomol Chem. 2015;13:9746-50 pubmed publisher
    ..of a ligand for the target protein and a ligand for ubiquitin ligase cellular inhibitor of apoptosis protein 1 (cIAP1). However, this technology has several limitations...
  50. Jiang Y, Meng Q, Chen B, Shen H, Yan B, Sun B. The small-molecule IAP antagonist AT406 inhibits pancreatic cancer cells in vitro and in vivo. Biochem Biophys Res Commun. 2016;478:293-299 pubmed publisher
    ..AT406 treatment caused degradation of IAP family proteins (cIAP1 and XIAP) and release of cytochrome C, leaving Bcl-2 unaffected in pancreatic cancer cells...
  51. Xia P, Qi Y. Cellular inhibitor of apoptosis protein-1 and survival of beta cells undergoing endoplasmic reticulum stress. Vitam Horm. 2014;95:269-98 pubmed publisher
    ..Specifically, we focus on the role of the cellular inhibitor of apoptosis protein-1 and propose a new model for understanding survival of beta cells undergoing ER stress. ..
  52. Mak P, Mak D, Ruvolo V, Jacamo R, Kornblau S, Kantarjian H, et al. Apoptosis repressor with caspase recruitment domain modulates second mitochondrial-derived activator of caspases mimetic-induced cell death through BIRC2/MAP3K14 signalling in acute myeloid leukaemia. Br J Haematol. 2014;167:376-84 pubmed publisher
    ..protein array analysis of 511 samples from newly diagnosed AML patients showed that BIRC2 (also termed cIAP1) and ARC were inversely correlated...
  53. Zhao T, Graber T, Jordan L, Cloutier M, Lewis S, Goulet I, et al. hnRNP A1 regulates UV-induced NF-kappaB signalling through destabilization of cIAP1 mRNA. Cell Death Differ. 2009;16:244-52 pubmed publisher
    b>cIAP1 is an important member of the inhibitor of apoptosis family of proteins and is involved in the regulation of the NF-kappaB-signalling pathway downstream of the TNF receptor...
  54. Stutz M, Ojaimi S, Allison C, Preston S, Arandjelovic P, Hildebrand J, et al. Necroptotic signaling is primed in Mycobacterium tuberculosis-infected macrophages, but its pathophysiological consequence in disease is restricted. Cell Death Differ. 2018;25:951-965 pubmed publisher
    ..remodeled the intracellular signaling landscape by upregulating MLKL, TNFR1, and ZBP1, whilst downregulating cIAP1, thereby establishing a strong pro-necroptotic milieu...
  55. Nakagawa Y, Abe S, Kurata M, Hasegawa M, Yamamoto K, Inoue M, et al. IAP family protein expression correlates with poor outcome of multiple myeloma patients in association with chemotherapy-induced overexpression of multidrug resistance genes. Am J Hematol. 2006;81:824-31 pubmed
    ..MDR1-expression after chemotherapy, those with a poor outcome exhibited significant increases in survivin, cIAP1, cIAP2, and XIAP expression by chemotherapy compared with those with a good prognosis...
  56. Werneburg B, Zoog S, Dang T, Kehry M, Crute J. Molecular characterization of CD40 signaling intermediates. J Biol Chem. 2001;276:43334-42 pubmed
    ..These results suggest that extracellular ligation of CD40 can be bypassed and that soluble trimerized CD40 complexes can be isolated and used to identify components that link CD40 with signaling pathways. ..
  57. Lopez J, Meier P. To fight or die - inhibitor of apoptosis proteins at the crossroad of innate immunity and death. Curr Opin Cell Biol. 2010;22:872-81 pubmed publisher
    ..Here, we discuss the latest insights into the ubiquitin-related roles of IAPs and how this contributes to the survival of cells and the organism. ..
  58. Huang Z, Su G, Hu W, Bi X, Zhang L, Wan G. The study on expression of CIAPIN1 interfering hepatocellular carcinoma cell proliferation and its mechanisms. Eur Rev Med Pharmacol Sci. 2017;21:3054-3060 pubmed
    ..This study was designed to investigate the effect of the cytokine-induced apoptosis inhibitor 1 (CIAPIN1) on hepatocellular carcinoma cell proliferation and invasion...
  59. Lin F, Ghislat G, Luo S, Renna M, Siddiqi F, Rubinsztein D. XIAP and cIAP1 amplifications induce Beclin 1-dependent autophagy through NFκB activation. Hum Mol Genet. 2015;24:2899-913 pubmed publisher
    Perturbations in autophagy and apoptosis are associated with cancer development. XIAP and cIAP1 are two members of the inhibitors of apoptosis protein family whose expression is elevated in different cancers...
  60. Vasilikos L, Spilgies L, Knop J, Wong W. Regulating the balance between necroptosis, apoptosis and inflammation by inhibitors of apoptosis proteins. Immunol Cell Biol. 2017;95:160-165 pubmed publisher
    ..necroptosis has been fast-forwarded by the use of Smac mimetics (SMs) to deplete or inhibit the IAPs, specifically cIAP1, cIAP2 and XIAP...
  61. Kester R, Donnell A, Lou Y, Remiszewski S, Lombardo L, Chen S, et al. Optimization of benzodiazepinones as selective inhibitors of the X-linked inhibitor of apoptosis protein (XIAP) second baculovirus IAP repeat (BIR2) domain. J Med Chem. 2013;56:7788-803 pubmed publisher
    ..While XIAP BIR3 inhibitors have previously been reported, they also inhibit cIAP1/2 and promote the release of TNF?, potentially limiting their therapeutic utility...
  62. Mukhopadhyay S, Naik P, Panda P, Sinha N, Das D, Bhutia S. Serum starvation induces anti-apoptotic cIAP1 to promote mitophagy through ubiquitination. Biochem Biophys Res Commun. 2016;479:940-946 pubmed publisher
    ..In this study, we established that serum starvation led to induction of cellular inhibitor of apoptosis protein-1 (cIAP1), which regulates mitophagy through ubiquitination...
  63. Paschall A, Zimmerman M, Torres C, Yang D, Chen M, Li X, et al. Ceramide targets xIAP and cIAP1 to sensitize metastatic colon and breast cancer cells to apoptosis induction to suppress tumor progression. BMC Cancer. 2014;14:24 pubmed publisher
    ..BV6 in sensitization of colon carcinoma cells to Fas-mediated apoptosis by inducing proteasomal degradation of cIAP1 and xIAP proteins...
  64. Tan B, Zammit N, Yam A, Slattery R, Walters S, Malle E, et al. Baculoviral inhibitors of apoptosis repeat containing (BIRC) proteins fine-tune TNF-induced nuclear factor ?B and c-Jun N-terminal kinase signalling in mouse pancreatic beta cells. Diabetologia. 2013;56:520-32 pubmed publisher
    ..Thus BIRC2 and BIRC3 fine-tune NF-?B and JNK signalling to ensure transcriptional responses are appropriately matched to extracellular inputs. This control is critical for the beta cell's stress response. ..
  65. Mei Y, Hahn A, Hu S, Yang X. The USP19 deubiquitinase regulates the stability of c-IAP1 and c-IAP2. J Biol Chem. 2011;286:35380-7 pubmed publisher
    ..These results suggest that the self-ubiquitin ligase activity of c-IAPs is inhibited by USP19 and implicate deubiquitinating enzymes in the regulation of IAP stability. ..
  66. Hinz M, Stilmann M, Arslan S, Khanna K, Dittmar G, Scheidereit C. A cytoplasmic ATM-TRAF6-cIAP1 module links nuclear DNA damage signaling to ubiquitin-mediated NF-?B activation. Mol Cell. 2010;40:63-74 pubmed publisher
    ..a TRAF-binding motif, ATM activates TRAF6, resulting in Ubc13-mediated K63-linked polyubiquitin synthesis and cIAP1 recruitment. The ATM-TRAF6-cIAP1 module stimulates TAB2-dependent TAK1 phosphorylation...