XIAP

Summary

Gene Symbol: XIAP
Description: X-linked inhibitor of apoptosis
Alias: API3, BIRC4, IAP-3, ILP1, MIHA, XLP2, hIAP-3, hIAP3, E3 ubiquitin-protein ligase XIAP, IAP-like protein, RING-type E3 ubiquitin transferase XIAP, X-linked IAP, X-linked inhibitor of apoptosis, E3 ubiquitin protein ligase, baculoviral IAP repeat-containing protein 4, inhibitor of apoptosis protein 3
Species: human
Products:     XIAP

Top Publications

  1. Krieg A, Correa R, Garrison J, Le Negrate G, Welsh K, Huang Z, et al. XIAP mediates NOD signaling via interaction with RIP2. Proc Natl Acad Sci U S A. 2009;106:14524-9 pubmed publisher
    ..In this report, we show that NOD signaling is dependent on XIAP, a member of the inhibitor of apoptosis protein (IAP) family...
  2. Oberoi T, Dogan T, Hocking J, Scholz R, Mooz J, Anderson C, et al. IAPs regulate the plasticity of cell migration by directly targeting Rac1 for degradation. EMBO J. 2012;31:14-28 pubmed publisher
    ..Here, we demonstrate X-linked IAP (XIAP) and cellular IAP1 (c-IAP1) directly bind to Rac1 in a nucleotide-independent manner to promote its ..
  3. Rigaud S, Fondaneche M, Lambert N, Pasquier B, Mateo V, Soulas P, et al. XIAP deficiency in humans causes an X-linked lymphoproliferative syndrome. Nature. 2006;444:110-4 pubmed
    ..Here, we identify mutations in the gene that encodes the X-linked inhibitor-of-apoptosis XIAP (also termed BIRC4) in patients with XLP from three families without mutations in SAP...
  4. Zhang S, Ding F, Luo A, Chen A, Yu Z, Ren S, et al. XIAP is highly expressed in esophageal cancer and its downregulation by RNAi sensitizes esophageal carcinoma cell lines to chemotherapeutics. Cancer Biol Ther. 2007;6:973-80 pubmed
    X-linked inhibitor of apoptosis protein (XIAP) is the most potent member of the IAP gene family in terms of its ability to inhibit caspases and suppress apoptosis...
  5. Deveraux Q, Roy N, Stennicke H, Van Arsdale T, Zhou Q, Srinivasula S, et al. IAPs block apoptotic events induced by caspase-8 and cytochrome c by direct inhibition of distinct caspases. EMBO J. 1998;17:2215-23 pubmed
    ..Human XIAP, cIAP1 and cIAP2 are direct inhibitors of at least two members of the caspase family of cell death proteases: ..
  6. Vucic D, Deshayes K, Ackerly H, Pisabarro M, Kadkhodayan S, Fairbrother W, et al. SMAC negatively regulates the anti-apoptotic activity of melanoma inhibitor of apoptosis (ML-IAP). J Biol Chem. 2002;277:12275-9 pubmed
    ..These results demonstrate the feasibility of using SMAC peptides as a way to sensitize IAP-expressing cells to pro-apoptotic stimuli such as chemotherapeutic agents. ..
  7. Holley C, Olson M, COLON RAMOS D, Kornbluth S. Reaper eliminates IAP proteins through stimulated IAP degradation and generalized translational inhibition. Nat Cell Biol. 2002;4:439-44 pubmed
  8. Hörnle M, Peters N, Thayaparasingham B, Vörsmann H, Kashkar H, Kulms D. Caspase-3 cleaves XIAP in a positive feedback loop to sensitize melanoma cells to TRAIL-induced apoptosis. Oncogene. 2011;30:575-87 pubmed publisher
    ..into catalytically inactive p21 by binding of the anti-apoptotic protein X-linked inhibitor of apoptosis protein (XIAP)...
  9. Martins L, Iaccarino I, Tenev T, Gschmeissner S, Totty N, Lemoine N, et al. The serine protease Omi/HtrA2 regulates apoptosis by binding XIAP through a reaper-like motif. J Biol Chem. 2002;277:439-44 pubmed
    ..Here we have identified the serine protease Omi/HtrA2 as a second mammalian XIAP-binding protein with a Reaper-like motif...

More Information

Publications121 found, 100 shown here

  1. Nakamura T, Wang L, Wong C, Scott F, Eckelman B, Han X, et al. Transnitrosylation of XIAP regulates caspase-dependent neuronal cell death. Mol Cell. 2010;39:184-95 pubmed publisher
    X-linked inhibitor of apoptosis (XIAP) is a potent antagonist of caspase apoptotic activity. XIAP also functions as an E3 ubiquitin ligase, targeting caspases for degradation...
  2. Liu J, Zhang D, Luo W, Yu J, Li J, Yu Y, et al. E3 ligase activity of XIAP RING domain is required for XIAP-mediated cancer cell migration, but not for its RhoGDI binding activity. PLoS ONE. 2012;7:e35682 pubmed publisher
    Although an increased expression level of XIAP is associated with cancer cell metastasis, the underlying molecular mechanisms remain largely unexplored...
  3. Sweeney M, Wang X, Park J, Liu Y, Pei D. Determination of the sequence specificity of XIAP BIR domains by screening a combinatorial peptide library. Biochemistry. 2006;45:14740-8 pubmed
    ..The X-chromosome-linked IAP (XIAP) contains three baculovirus IAP repeat (BIR) domains, which bind directly to the N-termini of target proteins ..
  4. 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. ..
  5. Gogada R, Prabhu V, Amadori M, Scott R, Hashmi S, Chandra D. Resveratrol induces p53-independent, X-linked inhibitor of apoptosis protein (XIAP)-mediated Bax protein oligomerization on mitochondria to initiate cytochrome c release and caspase activation. J Biol Chem. 2011;286:28749-60 pubmed publisher
    ..Here, we show that resveratrol induced p53-independent, X-linked inhibitor of apoptosis protein (XIAP)-mediated translocation of Bax to mitochondria where it underwent oligomerization to initiate apoptosis...
  6. 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
    ..These results suggest a novel and conserved mechanism by which IAPs block apoptosis through the degradation of death inducers. ..
  7. Mansouri A, Zhang Q, Ridgway L, Tian L, Claret F. Cisplatin resistance in an ovarian carcinoma is associated with a defect in programmed cell death control through XIAP regulation. Oncol Res. 2003;13:399-404 pubmed
    ..CDDP) treatment, we compared the effect of CDDP on expression of X-linked inhibitor of apoptosis protein (XIAP), a direct inhibitor of caspase-3, -7, and -9, Fas, Fas-ligand (Fas-L), and pro- and antiapoptotic proteins in a ..
  8. Dubrez Daloz L, Dupoux A, Cartier J. IAPs: more than just inhibitors of apoptosis proteins. Cell Cycle. 2008;7:1036-46 pubmed
    ..In mammals, BIRC4/XIAP, the most studied IAP member can directly inhibit the activity of caspase-3, 7 and 9...
  9. Damgaard R, Fiil B, Speckmann C, Yabal M, Zur Stadt U, Bekker Jensen S, et al. Disease-causing mutations in the XIAP BIR2 domain impair NOD2-dependent immune signalling. EMBO Mol Med. 2013;5:1278-95 pubmed publisher
    ..Mutations in XIAP cause X-linked lymphoproliferative syndrome type-2 (XLP2), an immunodeficiency associated with a potentially fatal deregulation of the immune system, whose aetiology is not ..
  10. Wilkinson J, Cepero E, Boise L, Duckett C. Upstream regulatory role for XIAP in receptor-mediated apoptosis. Mol Cell Biol. 2004;24:7003-14 pubmed
    X-linked inhibitor of apoptosis (XIAP) is an endogenous inhibitor of cell death that functions by suppressing caspases 3, 7, and 9...
  11. Damgaard R, Gyrd Hansen M. Inhibitor of apoptosis (IAP) proteins in regulation of inflammation and innate immunity. Discov Med. 2011;11:221-31 pubmed
    ..Recent evidence suggests that cIAP1, cIAP2, and XIAP facilitate ubiquitin-dependent signaling activated by these PRRs and mediate activation of nuclear factor-kappa B (..
  12. Srinivasula S, Hegde R, Saleh A, Datta P, Shiozaki E, Chai J, et al. A conserved XIAP-interaction motif in caspase-9 and Smac/DIABLO regulates caspase activity and apoptosis. Nature. 2001;410:112-6 pubmed
    X-linked inhibitor-of-apoptosis protein (XIAP) interacts with caspase-9 and inhibits its activity, whereas Smac (also known as DIABLO) relieves this inhibition through interaction with XIAP...
  13. 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
    ..survivin, a member of the inhibitor of apoptosis (IAP) gene family, associates with another IAP protein, XIAP, via conserved baculovirus IAP repeats...
  14. Huang Y, Park Y, Rich R, Segal D, Myszka D, Wu H. Structural basis of caspase inhibition by XIAP: differential roles of the linker versus the BIR domain. Cell. 2001;104:781-90 pubmed
    ..Here, we report the crystal structure of the complex between human caspase-7 and XIAP (BIR2 and the proceeding linker)...
  15. Birkey Reffey S, Wurthner J, Parks W, Roberts A, Duckett C. X-linked inhibitor of apoptosis protein functions as a cofactor in transforming growth factor-beta signaling. J Biol Chem. 2001;276:26542-9 pubmed
    X-linked inhibitor of apoptosis protein (XIAP) is a potent suppressor of apoptotic cell death, which functions by directly inhibiting caspases, the principal effectors of apoptosis...
  16. Nagi C, Xiao G, Li G, Genden E, Burstein D. Immunohistochemical detection of X-linked inhibitor of apoptosis in head and neck squamous cell carcinoma. Ann Diagn Pathol. 2007;11:402-6 pubmed
    The X-linked inhibitor of apoptosis (XIAP) is the most potent member of the IAP group of structurally related caspase inhibitors...
  17. Gallardo Pérez J, Espinosa M, Ceballos Cancino G, Daniel A, Rodriguez Enriquez S, Aviles A, et al. NF-kappa B is required for the development of tumor spheroids. J Cell Biochem. 2009;108:169-80 pubmed publisher
    ..In this work, we found a significant increase in the activity and expression of NF-kappaB and its downstream target XIAP (X-linked IAP) in cancer cells grown as multi-cellular tumor spheroids...
  18. Van Themsche C, Chaudhry P, Leblanc V, Parent S, Asselin E. XIAP gene expression and function is regulated by autocrine and paracrine TGF-beta signaling. Mol Cancer. 2010;9:216 pubmed publisher
    X-linked inhibitor of apoptosis protein (XIAP) is often overexpressed in cancer cells, where it plays a key role in survival and also promotes invasiveness...
  19. Rajcan Separovic E, Liston P, Lefebvre C, Korneluk R. Assignment of human inhibitor of apoptosis protein (IAP) genes xiap, hiap-1, and hiap-2 to chromosomes Xq25 and 11q22-q23 by fluorescence in situ hybridization. Genomics. 1996;37:404-6 pubmed
  20. Hao Y, Sekine K, Kawabata A, Nakamura H, Ishioka T, Ohata H, et al. Apollon ubiquitinates SMAC and caspase-9, and has an essential cytoprotection function. Nat Cell Biol. 2004;6:849-60 pubmed
    ..Furthermore, the IAP-binding motif of SMAC was required to induce apoptosis in Apollon-deficient cells. These results suggest that Apollon has an essential function in preventing SMAC-induced apoptosis. ..
  21. Fang Y, Yu Y, Hou Q, Zheng X, Zhang M, Zhang D, et al. The Chinese herb isolate isorhapontigenin induces apoptosis in human cancer cells by down-regulating overexpression of antiapoptotic protein XIAP. J Biol Chem. 2012;287:35234-43 pubmed publisher
    ..by marked apoptotic induction as well as down-regulation of the X-linked inhibitor of apoptosis protein (XIAP)...
  22. Liu W, Hsiao H, Tsou W, Lai M. Notch inhibits apoptosis by direct interference with XIAP ubiquitination and degradation. EMBO J. 2007;26:1660-9 pubmed
    ..intracellular domain could partly be attributed to a selective increase of X-linked inhibitor of apoptosis protein (XIAP). We further found that Notch intracellular domain inhibited the degradation of XIAP during apoptosis...
  23. Walsh J, Cullen S, Sheridan C, Lüthi A, Gerner C, Martin S. Executioner caspase-3 and caspase-7 are functionally distinct proteases. Proc Natl Acad Sci U S A. 2008;105:12815-9 pubmed publisher
    ..show that caspase-3 and caspase-7 exhibit differential activity toward multiple substrate proteins, including Bid, XIAP, gelsolin, caspase-6, and cochaperone p23...
  24. Moussata D, Amara S, Siddeek B, Decaussin M, Hehlgans S, Paul Bellon R, et al. XIAP as a radioresistance factor and prognostic marker for radiotherapy in human rectal adenocarcinoma. Am J Pathol. 2012;181:1271-8 pubmed publisher
    ..active caspase 3, 8, and 9 and DIABLO (direct inhibitor of apoptosis-binding protein with low pI); anti-apoptotic: XIAP (X-linked inhibitor of apoptosis)] are involved, we analyzed their profile in radioresistant (SW480) and ..
  25. Chai J, Shiozaki E, Srinivasula S, Wu Q, Datta P, Alnemri E, et al. Structural basis of caspase-7 inhibition by XIAP. Cell. 2001;104:769-80 pubmed
    ..Here we present the crystal structure of caspase-7 in complex with a potent inhibitory fragment from XIAP at 2.45 A resolution...
  26. Wilkinson J, Wilkinson A, Galban S, Csomos R, Duckett C. Apoptosis-inducing factor is a target for ubiquitination through interaction with XIAP. Mol Cell Biol. 2008;28:237-47 pubmed
    X-linked inhibitor of apoptosis (XIAP) is an inhibitor of apoptotic cell death that protects cells by caspase-dependent and independent mechanisms...
  27. Yang W, Cooke M, Duckett C, Yang X, Dorsey J. Distinctive effects of the cellular inhibitor of apoptosis protein c-IAP2 through stabilization by XIAP in glioblastoma multiforme cells. Cell Cycle. 2014;13:992-1005 pubmed publisher
    ..When overexpressed, X-linked IAP (XIAP) enhanced expression of ectopic c-IAP2, but not c-IAP1, and endogenous c-IAP2 levels were reduced once XIAP ..
  28. Riedl S, Renatus M, Schwarzenbacher R, Zhou Q, Sun C, Fesik S, et al. Structural basis for the inhibition of caspase-3 by XIAP. Cell. 2001;104:791-800 pubmed
    ..The main endogenous inhibitors are members of the IAP family and are exemplified by XIAP, which regulates the initiator caspase-9, and the executioner caspases-3 and -7...
  29. Rehm M, Huber H, Dussmann H, Prehn J. Systems analysis of effector caspase activation and its control by X-linked inhibitor of apoptosis protein. EMBO J. 2006;25:4338-49 pubmed
    ..a critical role for caspase-3-dependent feedback signalling and the X-linked-inhibitor-of-apoptosis-protein (XIAP), but a less prominent role for the XIAP antagonist Smac...
  30. 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
    ..b>XIAP mediates activation of the upstream IKK kinase, TAK1, and couples activated TAK1 to the IKK complex...
  31. Liu Z, Shen J, Pu K, Katus H, Plöger F, Tiefenbacher C, et al. GDF5 and BMP2 inhibit apoptosis via activation of BMPR2 and subsequent stabilization of XIAP. Biochim Biophys Acta. 2009;1793:1819-27 pubmed publisher
    ..GDF5 and BMP2 stimulate the interaction of BMPR-2 with XIAP thereby reducing the ubiquitination of XIAP, which results in enhanced protein stability...
  32. Song Z, Yao X, Wu M. Direct interaction between survivin and Smac/DIABLO is essential for the anti-apoptotic activity of survivin during taxol-induced apoptosis. J Biol Chem. 2003;278:23130-40 pubmed
    ..We also identified that the co-presence of Smac/DIABLO and XIAP was required for Survivin to inhibit caspase cleavage in a cell-free system...
  33. Ndozangue Touriguine O, Sebbagh M, Merino D, Micheau O, Bertoglio J, Breard J. A mitochondrial block and expression of XIAP lead to resistance to TRAIL-induced apoptosis during progression to metastasis of a colon carcinoma. Oncogene. 2008;27:6012-22 pubmed publisher
    ..that, in contrast to SW480 cells, the SW620 cell line expresses high amounts of X-linked inhibitor of apoptosis (XIAP)...
  34. Pachlopnik Schmid J, Canioni D, Moshous D, Touzot F, Mahlaoui N, Hauck F, et al. Clinical similarities and differences of patients with X-linked lymphoproliferative syndrome type 1 (XLP-1/SAP deficiency) versus type 2 (XLP-2/XIAP deficiency). Blood. 2011;117:1522-9 pubmed publisher
    ..XLP type 1 (XLP-1) is caused by mutations in the gene SH2D1A (also named SAP), whereas mutations in the gene XIAP underlie XLP type 2 (XLP-2)...
  35. Yamaguchi K, Nagai S, Ninomiya Tsuji J, Nishita M, Tamai K, Irie K, et al. XIAP, a cellular member of the inhibitor of apoptosis protein family, links the receptors to TAB1-TAK1 in the BMP signaling pathway. EMBO J. 1999;18:179-87 pubmed
    ..The human X-chromosome-linked inhibitor of apoptosis protein (XIAP) was isolated as a TAB1-binding protein...
  36. Neil J, Tian M, Schiemann W. X-linked inhibitor of apoptosis protein and its E3 ligase activity promote transforming growth factor-{beta}-mediated nuclear factor-{kappa}B activation during breast cancer progression. J Biol Chem. 2009;284:21209-17 pubmed publisher
    ..We show here that X-linked inhibitor of apoptosis protein (xIAP) is essential for the ability of TGF-beta to stimulate nuclear factor-kappaB (NF-kappaB) in metastatic 4T1 breast ..
  37. Nakatani Y, Kleffmann T, Linke K, Condon S, Hinds M, Day C. Regulation of ubiquitin transfer by XIAP, a dimeric RING E3 ligase. Biochem J. 2013;450:629-38 pubmed publisher
    ..that E2 conjugated ubiquitin contacts the RING homodimer interface of the IAP (inhibitor of apoptosis) proteins, XIAP (X-linked IAP) and cIAP (cellular IAP) 2...
  38. Shiraki K, Sugimoto K, Yamanaka Y, Yamaguchi Y, Saitou Y, Ito K, et al. Overexpression of X-linked inhibitor of apoptosis in human hepatocellular carcinoma. Int J Mol Med. 2003;12:705-8 pubmed
    The X-linked inhibitor of apoptosis (XIAP) is a member of a novel family of inhibitors of apoptosis...
  39. Liu Z, Sun C, Olejniczak E, Meadows R, Betz S, Oost T, et al. Structural basis for binding of Smac/DIABLO to the XIAP BIR3 domain. Nature. 2000;408:1004-8 pubmed
    ..recognition between Smac and the IAPs, we determined the solution structure of the BIR3 domain of X-linked IAP (XIAP) complexed with a functionally active nine-residue peptide derived from the N terminus of Smac...
  40. Scott F, Denault J, Riedl S, Shin H, Renatus M, Salvesen G. XIAP inhibits caspase-3 and -7 using two binding sites: evolutionarily conserved mechanism of IAPs. EMBO J. 2005;24:645-55 pubmed
    The X-linked inhibitor of apoptosis protein (XIAP) uses its second baculovirus IAP repeat domain (BIR2) to inhibit the apoptotic executioner caspase-3 and -7...
  41. Hu Y, Cherton Horvat G, Dragowska V, Baird S, Korneluk R, Durkin J, et al. Antisense oligonucleotides targeting XIAP induce apoptosis and enhance chemotherapeutic activity against human lung cancer cells in vitro and in vivo. Clin Cancer Res. 2003;9:2826-36 pubmed
    ..X-linked inhibitor of apoptosis (XIAP), is the most potent member of the IAP gene family in terms of its ability to inhibit caspases and suppress ..
  42. Duckett C, Nava V, Gedrich R, Clem R, van Dongen J, Gilfillan M, et al. A conserved family of cellular genes related to the baculovirus iap gene and encoding apoptosis inhibitors. EMBO J. 1996;15:2685-94 pubmed
    ..Together these data suggest that iap and related cellular genes play an evolutionarily conserved role in the regulation of apoptosis. ..
  43. Cao Z, Zhang R, Li J, Huang H, Zhang D, Zhang J, et al. X-linked inhibitor of apoptosis protein (XIAP) regulation of cyclin D1 protein expression and cancer cell anchorage-independent growth via its E3 ligase-mediated protein phosphatase 2A/c-Jun axis. J Biol Chem. 2013;288:20238-47 pubmed publisher
    The X-linked inhibitor of apoptosis protein (XIAP) is a well known potent inhibitor of apoptosis; however, it is also involved in other cancer cell biological behavior...
  44. Sauerwald T, Betenbaugh M, Oyler G. Inhibiting apoptosis in mammalian cell culture using the caspase inhibitor XIAP and deletion mutants. Biotechnol Bioeng. 2002;77:704-16 pubmed
    ..b>XIAP is the most potent caspase inhibitor encoded in the mammalian genome...
  45. Van Themsche C, Lafontaine L, Asselin E. X-linked inhibitor of apoptosis protein levels and protein kinase C activity regulate the sensitivity of human endometrial carcinoma cells to tumor necrosis factor alpha-induced apoptosis. Endocrinology. 2008;149:3789-98 pubmed publisher
    ..apoptosis in endometrial carcinoma cells, and examined a putative role for X-linked inhibitor of apoptosis protein (XIAP) in regulating cellular sensitivity to the cytokine...
  46. Mufti A, Burstein E, Duckett C. XIAP: cell death regulation meets copper homeostasis. Arch Biochem Biophys. 2007;463:168-74 pubmed
    X-linked inhibitor of apoptosis (XIAP), traditionally known as an anti-apoptotic protein, has recently been shown to be involved in copper homeostasis...
  47. Van Themsche C, Leblanc V, Parent S, Asselin E. X-linked inhibitor of apoptosis protein (XIAP) regulates PTEN ubiquitination, content, and compartmentalization. J Biol Chem. 2009;284:20462-6 pubmed publisher
    ..The phosphorylation of Akt has previously been shown to be promoted by X-linked inhibitor of apoptosis protein (XIAP), another antiapoptotic protein dictating the fate of normal and cancer cells...
  48. Nowak D, Boehrer S, Brieger A, Kim S, Schaaf S, Hoelzer D, et al. Upon drug-induced apoptosis in lymphoma cells X-linked inhibitor of apoptosis (XIAP) translocates from the cytosol to the nucleus. Leuk Lymphoma. 2004;45:1429-36 pubmed
    The X-linked inhibitor of apoptosis (XIAP) and cellular inhibitor of apoptosis-1 (cIAP-1) are emerging as versatile proteins in programmed cell death with a scope of possible functions reaching far beyond their well known inhibitory ..
  49. Gu L, Li F, Zhao L, Liu Y, Zang X, Wang T, et al. BRAFV600E mutation and X-linked inhibitor of apoptosis expression in papillary thyroid carcinoma. Thyroid. 2009;19:347-54 pubmed publisher
    ..genetic alteration in papillary thyroid carcinoma (PTC), while overexpression of X-linked inhibitor of apoptosis (XIAP) has been found in various tumors...
  50. Liu J, Zhang D, Luo W, Yu Y, Yu J, Li J, et al. 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. 2011;286:15630-40 pubmed publisher
    X-linked inhibitor of apoptosis protein (XIAP) overexpression has been found to be associated with malignant cancer progression and aggression in individuals with many types of cancers...
  51. 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;137:125-32 pubmed
    ..Here we show that X-linked IAP (XIAP) mediates the polyubiquitination of caspase-9 and Smac...
  52. 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
    To identify proteins that bind mammalian IAP homolog A (MIHA, also known as XIAP), we used coimmuno-precipitation and 2D immobilized pH gradient/SDS PAGE, followed by electrospray ionization tandem mass spectrometry...
  53. Burstein E, Ganesh L, Dick R, van De Sluis B, Wilkinson J, Klomp L, et al. A novel role for XIAP in copper homeostasis through regulation of MURR1. EMBO J. 2004;23:244-54 pubmed
    b>XIAP is a potent suppressor of apoptosis that directly inhibits specific members of the caspase family of cysteine proteases. Here we demonstrate a novel role for XIAP in the control of intracellular copper levels...
  54. Ramp U, Krieg T, Caliskan E, Mahotka C, Ebert T, Willers R, et al. XIAP expression is an independent prognostic marker in clear-cell renal carcinomas. Hum Pathol. 2004;35:1022-8 pubmed
    ..b>XIAP is considered to be the most potent caspase inhibitor of all known IAP (inhibitor of apoptosis) family members...
  55. Tenev T, Zachariou A, Wilson R, Ditzel M, Meier P. IAPs are functionally non-equivalent and regulate effector caspases through distinct mechanisms. Nat Cell Biol. 2005;7:70-7 pubmed
    ..Whereas XIAP binds directly to the active-site pockets of effector caspases, we find that regulation of effector caspases by ..
  56. Lin S, Huang Y, Lo Y, Lu M, Wu H. Crystal structure of the BIR1 domain of XIAP in two crystal forms. J Mol Biol. 2007;372:847-54 pubmed
    X-linked inhibitor of apoptosis (XIAP) is a potent negative regulator of apoptosis. It also plays a role in BMP signaling, TGF-beta signaling, and copper homeostasis...
  57. Shi Y, Ding W, Zhou J, He J, Xu Y, Gambotto A, et al. Expression of X-linked inhibitor-of-apoptosis protein in hepatocellular carcinoma promotes metastasis and tumor recurrence. Hepatology. 2008;48:497-507 pubmed publisher
    ..Subsequent investigation revealed that increased expression of X-linked inhibitor-of-apoptosis protein (XIAP) was correlated with the resistance to apoptosis and enhanced invasiveness in vitro, which could contribute to ..
  58. Vogler M, Walczak H, Stadel D, Haas T, Genze F, Jovanovic M, et al. Targeting XIAP bypasses Bcl-2-mediated resistance to TRAIL and cooperates with TRAIL to suppress pancreatic cancer growth in vitro and in vivo. Cancer Res. 2008;68:7956-65 pubmed publisher
    ..Here, we report that the combination of X-linked inhibitor of apoptosis (XIAP) inhibition and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is an effective approach to trigger ..
  59. Desplanques G, Giuliani N, Delsignore R, Rizzoli V, Bataille R, Barillé Nion S. Impact of XIAP protein levels on the survival of myeloma cells. Haematologica. 2009;94:87-93 pubmed publisher
    b>XIAP is the best characterized and the most potent direct endogenous caspase inhibitor and is considered a key actor in the control of apoptotic threshold in cancer cells...
  60. Aird K, Ghanayem R, Peplinski S, Lyerly H, Devi G. X-linked inhibitor of apoptosis protein inhibits apoptosis in inflammatory breast cancer cells with acquired resistance to an ErbB1/2 tyrosine kinase inhibitor. Mol Cancer Ther. 2010;9:1432-42 pubmed publisher
    ..IBC cells, we identified the overexpression of an antiapoptotic protein, X-linked inhibitor of apoptosis protein (XIAP), in acquired resistance to GW583340 in both ErbB2-overexpressing SUM190 and ErbB1-activated SUM149 cell lines ..
  61. Liston P, Roy N, Tamai K, Lefebvre C, Baird S, Cherton Horvat G, et al. Suppression of apoptosis in mammalian cells by NAIP and a related family of IAP genes. Nature. 1996;379:349-53 pubmed
    ..The human iap genes have a distinct but overlapping pattern of expression in fetal and adult tissues. These proteins significantly increase the number of known apoptotic suppressors. ..
  62. Wu G, Chai J, Suber T, Wu J, Du C, Wang X, et al. Structural basis of IAP recognition by Smac/DIABLO. Nature. 2000;408:1008-12 pubmed
    ..Here we report the high-resolution crystal structure of Smac/DIABLO complexed with the third BIR domain (BIR3) of XIAP. Our results show that the N-terminal four residues (Ala-Val-Pro-Ile) in Smac/DIABLO recognize a surface groove on ..
  63. Kobayashi S, Yamashita K, Takeoka T, Ohtsuki T, Suzuki Y, Takahashi R, et al. Calpain-mediated X-linked inhibitor of apoptosis degradation in neutrophil apoptosis and its impairment in chronic neutrophilic leukemia. J Biol Chem. 2002;277:33968-77 pubmed
    ..Here, we found that calpains cleave the X-linked inhibitor of apoptosis (XIAP) in vitro, producing fragments that are unable to inhibit caspase-3...
  64. Fu J, Jin Y, Arend L. Smac3, a novel Smac/DIABLO splicing variant, attenuates the stability and apoptosis-inhibiting activity of X-linked inhibitor of apoptosis protein. J Biol Chem. 2003;278:52660-72 pubmed
    X-linked inhibitor of apoptosis protein (XIAP), the most potent member of the inhibitor of apoptosis protein (IAP) family, plays a crucial role in the regulation of apoptosis...
  65. Ohnishi K, Scuric Z, Schiestl R, Okamoto N, Takahashi A, Ohnishi T. siRNA targeting NBS1 or XIAP increases radiation sensitivity of human cancer cells independent of TP53 status. Radiat Res. 2006;166:454-62 pubmed
    ..In addition, radiation-induced expression of the transcription factor NF-kappaB (NFKB) and XIAP (X-chromosome-linked inhibitor of apoptosis protein) was suppressed by NBS1-siRNA...
  66. 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. ..
  67. 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
    ..When deubiquitinated by AEG40730 treatment, RIP1 binds caspase-8 and induces apoptosis. These findings provide insights into the function of the IAPs and provide new therapeutic opportunities in the treatment of cancer. ..
  68. Marsh R, Villanueva J, Kim M, Zhang K, Marmer D, Risma K, et al. Patients with X-linked lymphoproliferative disease due to BIRC4 mutation have normal invariant natural killer T-cell populations. Clin Immunol. 2009;132:116-23 pubmed publisher
    ..disease (XLP) due to SH2D1A mutation, and are reported to be decreased in patients with XLP due to BIRC4 mutations...
  69. Garrison J, Correa R, Gerlic M, Yip K, Krieg A, Tamble C, et al. ARTS and Siah collaborate in a pathway for XIAP degradation. Mol Cell. 2011;41:107-16 pubmed publisher
    ARTS (apoptosis-related protein in the TGF-? signaling pathway) is a mitochondrial protein that binds XIAP (X-linked inhibitor of apoptosis protein) upon entering the cytosol, thus promoting cell death...
  70. 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
    ..This function is not conserved for cIAP2 and XIAP, which are cytoplasmic proteins...
  71. Yu J, Zhang D, Liu J, Li J, Yu Y, Wu X, et al. RhoGDI SUMOylation at Lys-138 increases its binding activity to Rho GTPase and its inhibiting cancer cell motility. J Biol Chem. 2012;287:13752-60 pubmed publisher
    ..Our previous studies reported that X-linked inhibitor of apoptosis protein (XIAP) interacted with RhoGDI via its RING domain and negatively modulated RhoGDI SUMOylation and HCT116 cancer cell ..
  72. Takahashi R, Deveraux Q, Tamm I, Welsh K, Assa Munt N, Salvesen G, et al. A single BIR domain of XIAP sufficient for inhibiting caspases. J Biol Chem. 1998;273:7787-90 pubmed
    ..Some IAP family proteins, including XIAP, cIAP-1, and cIAP-2, can bind and directly inhibit selected caspases, a group of intracellular cell death proteases...
  73. Shiozaki E, Chai J, Rigotti D, Riedl S, Li P, Srinivasula S, et al. Mechanism of XIAP-mediated inhibition of caspase-9. Mol Cell. 2003;11:519-27 pubmed
    ..reports the crystal structure of caspase-9 in an inhibitory complex with the third baculoviral IAP repeat (BIR3) of XIAP at 2.4 A resolution. The structure reveals that the BIR3 domain forms a heterodimer with a caspase-9 monomer...
  74. Huang Y, Rich R, Myszka D, Wu H. Requirement of both the second and third BIR domains for the relief of X-linked inhibitor of apoptosis protein (XIAP)-mediated caspase inhibition by Smac. J Biol Chem. 2003;278:49517-22 pubmed
    ..X-linked IAP (XIAP) contains three BIR domains and directly inhibits effector caspases such as caspase-7 via a linker_BIR2 fragment ..
  75. Silke J, Kratina T, Ekert P, Pakusch M, Vaux D. Unlike Diablo/smac, Grim promotes global ubiquitination and specific degradation of X chromosome-linked inhibitor of apoptosis (XIAP) and neither cause apoptosis. J Biol Chem. 2004;279:4313-21 pubmed
    ..Although they have the same IAP binding specificity, only Grim promoted XIAP ubiquitination and degradation...
  76. Samuel T, Okada K, Hyer M, Welsh K, Zapata J, Reed J. cIAP1 Localizes to the nuclear compartment and modulates the cell cycle. Cancer Res. 2005;65:210-8 pubmed
    ..Unlike family member X-linked IAP (XIAP), which was predominantly cytoplasmic, the cIAP1 protein localized almost exclusively to nuclei in cells, as ..
  77. Eckelman B, Salvesen G, Scott F. Human inhibitor of apoptosis proteins: why XIAP is the black sheep of the family. EMBO Rep. 2006;7:988-94 pubmed
    ..The most intensively studied family member, X-linked IAP (XIAP), is a potent inhibitor of caspase activity; hence, it is generally assumed that direct caspase inhibition is an ..
  78. 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
    ..Moreover, the UBA domain is required for XIAP and cIAP2-MALT1 to activate NF-kappaB...
  79. Owens T, Foster F, Valentijn A, Gilmore A, Streuli C. Role for X-linked Inhibitor of apoptosis protein upstream of mitochondrial permeabilization. J Biol Chem. 2010;285:1081-8 pubmed publisher
    ..Here, we identify a novel and unexpected function for X-linked inhibitor of apoptosis (XIAP) that occurs when apoptosis is triggered under physiological conditions...
  80. Kashkar H. X-linked inhibitor of apoptosis: a chemoresistance factor or a hollow promise. Clin Cancer Res. 2010;16:4496-502 pubmed publisher
    The X-linked inhibitor of apoptosis (XIAP) is the only cellular protein that has evolved to potently inhibit the enzymatic activity of mammalian caspases and promotes resistance to apoptosis...
  81. Liston P, Fong W, Kelly N, Toji S, Miyazaki T, Conte D, et al. Identification of XAF1 as an antagonist of XIAP anti-Caspase activity. Nat Cell Biol. 2001;3:128-33 pubmed
    ..Here we have isolated the protein XIAP-associated factor 1 (XAF1) on the basis of its ability to bind XIAP, a member of the IAP family...
  82. Tamm I, Richter S, Oltersdorf D, Creutzig U, Harbott J, Scholz F, et al. High expression levels of x-linked inhibitor of apoptosis protein and survivin correlate with poor overall survival in childhood de novo acute myeloid leukemia. Clin Cancer Res. 2004;10:3737-44 pubmed
    ..of apoptosis-regulating proteins [CD95, Bcl-2, Bax, Bcl-xL, procaspase-3, X-linked inhibitor of apoptosis protein (XIAP), cellular inhibitor of apoptosis protein-1 (cIAP-1), survivin]. XIAP (P < 0...
  83. Potts M, Vaughn A, McDonough H, Patterson C, Deshmukh M. Reduced Apaf-1 levels in cardiomyocytes engage strict regulation of apoptosis by endogenous XIAP. J Cell Biol. 2005;171:925-30 pubmed
    Overexpression studies have identified X-linked inhibitor of apoptosis protein (XIAP) as a potent inhibitor of caspases. However, the exact function of endogenous XIAP in regulating mammalian apoptosis is less clear...
  84. Kang H, Lee S, Chae M, Lee W, Cha S, Kim C, et al. Identification of polymorphisms in the XIAP gene and analysis of association with lung cancer risk in a Korean population. Cancer Genet Cytogenet. 2008;180:6-13 pubmed
    The X-linked inhibitor of apoptosis protein (XIAP) is a potent mammalian IAP, and has been shown to play an important role in development and progression of cancer...
  85. Gagnon V, Van Themsche C, Turner S, Leblanc V, Asselin E. Akt and XIAP regulate the sensitivity of human uterine cancer cells to cisplatin, doxorubicin and taxol. Apoptosis. 2008;13:259-71 pubmed
    We have investigated the interrelationship between two anti-apoptotic factors, XIAP and Akt, and their role in chemoresistance of uterine cancer cells...
  86. Dogan T, Harms G, Hekman M, Karreman C, Oberoi T, Alnemri E, et al. X-linked and cellular IAPs modulate the stability of C-RAF kinase and cell motility. Nat Cell Biol. 2008;10:1447-55 pubmed publisher
    ..Here we demonstrate that XIAP and c-IAPs bind directly to C-RAF kinase and that siRNA-mediated silencing of XIAP and c-IAPs leads to ..
  87. Damgaard R, Nachbur U, Yabal M, Wong W, Fiil B, Kastirr M, et al. The ubiquitin ligase XIAP recruits LUBAC for NOD2 signaling in inflammation and innate immunity. Mol Cell. 2012;46:746-58 pubmed publisher
    ..X-linked Inhibitor of Apoptosis (XIAP) is implicated in the control of bacterial infections, and mutations in XIAP are causally linked to ..
  88. Huang X, Wu Z, Mei Y, Wu M. XIAP inhibits autophagy via XIAP-Mdm2-p53 signalling. EMBO J. 2013;32:2204-16 pubmed publisher
    ..Upregulation of X-linked inhibitor of apoptosis (XIAP) has been associated to a variety of human cancers, yet the underlying mechanisms remain obscure...
  89. MacFarlane M, Merrison W, Bratton S, Cohen G. Proteasome-mediated degradation of Smac during apoptosis: XIAP promotes Smac ubiquitination in vitro. J Biol Chem. 2002;277:36611-6 pubmed
    ..As the RING finger domain of XIAP possesses ubiquitin-protein ligase activity and XIAP binds tightly to mature Smac, an in vitro ubiquitination assay ..
  90. Holcik M, Gordon B, Korneluk R. The internal ribosome entry site-mediated translation of antiapoptotic protein XIAP is modulated by the heterogeneous nuclear ribonucleoproteins C1 and C2. Mol Cell Biol. 2003;23:280-8 pubmed
    The X-chromosome-linked inhibitor of apoptosis, XIAP, is the most powerful and ubiquitous intrinsic inhibitor of apoptosis...
  91. Wang X, Zhu C, Wang X, Hagberg H, Korhonen L, Sandberg M, et al. X-linked inhibitor of apoptosis (XIAP) protein protects against caspase activation and tissue loss after neonatal hypoxia-ischemia. Neurobiol Dis. 2004;16:179-89 pubmed
    Nine-day-old transgenic XIAP overexpressing (TG-XIAP) and wild-type mice were subjected to left carotid artery ligation and 10% O(2) for 60 min, leading to widespread infarctions in the ipsilateral hemisphere during reperfusion...
  92. 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
    ..Cross control of protein levels by RING domains may therefore enable their levels to be manipulated therapeutically. ..