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. 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. ..
  3. 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
  4. 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)...
  5. 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...
  6. 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...
  7. 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 ..
  8. 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...
  9. 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...
  10. 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 ..

Detail Information

Publications95

  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. 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. ..
  3. 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
  4. 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)...
  5. 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...
  6. 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...
  7. 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 ..
  8. 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...
  9. 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...
  10. 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 ..
  11. 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...
  12. 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...
  13. 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...
  14. 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...
  15. 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)...
  16. 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)...
  17. 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...
  18. 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...
  19. 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 ..
  20. 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...
  21. 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...
  22. 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...
  23. 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...
  24. 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. ..
  25. 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...
  26. 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...
  27. 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 ..
  28. 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...
  29. 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...
  30. 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...
  31. 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 ..
  32. 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...
  33. 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 ..
  34. 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 ..
  35. 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...
  36. 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 ..
  37. 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...
  38. 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...
  39. 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...
  40. 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. ..
  41. 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...
  42. 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...
  43. 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...
  44. 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 ..
  45. 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...
  46. 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 ..
  47. 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. ..
  48. 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. ..
  49. 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...
  50. 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...
  51. 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 ..
  52. 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...
  53. 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...
  54. 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 ..
  55. 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...
  56. 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...
  57. 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 ..
  58. 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...
  59. 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...
  60. 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...
  61. 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 ..
  62. 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...
  63. 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...
  64. 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...
  65. 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...
  66. 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...
  67. 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 ..
  68. 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
    ..These results show that TRAF2 has anti-apoptotic signaling roles in addition to promoting NF-kappaB signaling and that efficient activation of NF-kappaB by TNFR1 requires the recruitment of cIAP1/2 by TRAF2. ..
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    The X-chromosome-linked inhibitor of apoptosis, XIAP, is the most powerful and ubiquitous intrinsic inhibitor of apoptosis...
  70. 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. ..
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    b>XIAP, the X-linked inhibitor of apoptosis, is the best example of an endogenous cellular suppressor of apoptosis...
  72. 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 ..
  73. Wu Z, Wong E, Shi Y, Niu J, Chen Z, Miyamoto S, et al. ATM- and NEMO-dependent ELKS ubiquitination coordinates TAK1-mediated IKK activation in response to genotoxic stress. Mol Cell. 2010;40:75-86 pubmed publisher
    ..K63-linked polyubiquitination of ELKS, dependent on the ubiquitin ligase XIAP and the conjugating enzyme UBC13, allows ELKS association with TAK1 via its ubiquitin-binding subunits TAB2/3...
  74. 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...
  75. Lewis E, Wilkinson A, Davis N, Horita D, Wilkinson J. Nondegradative ubiquitination of apoptosis inducing factor (AIF) by X-linked inhibitor of apoptosis at a residue critical for AIF-mediated chromatin degradation. Biochemistry. 2011;50:11084-96 pubmed publisher
    ..X-linked inhibitor of apoptosis (XIAP) is an endogenous inhibitor of caspases that also regulates several caspase-independent signaling pathways...
  76. Verhagen A, Silke J, Ekert P, Pakusch M, Kaufmann H, Connolly L, et al. HtrA2 promotes cell death through its serine protease activity and its ability to antagonize inhibitor of apoptosis proteins. J Biol Chem. 2002;277:445-54 pubmed
    ..that HtrA2, a mammalian homologue of the Escherichia coli heat shock-inducible protein HtrA, can bind to MIHA/XIAP, MIHB, and baculoviral OpIAP but not survivin...
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    The X-linked inhibitor of apoptosis protein (XIAP) is associated with cell survival by blocking caspase-mediated apoptosis...
  79. Condé C, Rambout X, Lebrun M, Lecat A, Di Valentin E, Dequiedt F, et al. The inositol phosphatase SHIP-1 inhibits NOD2-induced NF-?B activation by disturbing the interaction of XIAP with RIP2. PLoS ONE. 2012;7:e41005 pubmed publisher
    ..This negative regulation relies on its interaction with XIAP. Indeed, we observed that XIAP is an essential mediator of the NOD2 signaling pathway that enables proper NF-?B ..
  80. O Connor C, Anguissola S, Huber H, Dussmann H, Prehn J, Rehm M. Intracellular signaling dynamics during apoptosis execution in the presence or absence of X-linked-inhibitor-of-apoptosis-protein. Biochim Biophys Acta. 2008;1783:1903-13 pubmed publisher
    X-linked-inhibitor-of-apoptosis-protein (XIAP) is the most potent intracellular inhibitor of caspases-9, -3 and -7...
  81. Sensintaffar J, Scott F, Peach R, Hager J. XIAP is not required for human tumor cell survival in the absence of an exogenous death signal. BMC Cancer. 2010;10:11 pubmed publisher
    The X-linked Inhibitor of Apoptosis (XIAP) has attracted much attention as a cancer drug target...
  82. 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...
  83. Varfolomeev E, Alicke B, Elliott J, Zobel K, West K, Wong H, et al. X chromosome-linked inhibitor of apoptosis regulates cell death induction by proapoptotic receptor agonists. J Biol Chem. 2009;284:34553-60 pubmed publisher
    ..However, knockdown of X chromosome-linked IAP (XIAP) or antagonism of XIAP allows FasL or DR5 agonist antibody to induce activation of effector caspases efficiently ..
  84. Xiao G, Unger P, Burstein D. Immunohistochemical detection of X-linked inhibitor of apoptosis (XIAP) in neoplastic and other thyroid disorders. Ann Diagn Pathol. 2007;11:235-40 pubmed
    The X-linked inhibitor of apoptosis (XIAP) is the most potent of the inhibitors of apoptosis, a group of related caspase inhibitors...
  85. Shibata T, Mahotka C, Wethkamp N, Heikaus S, Gabbert H, Ramp U. Disturbed expression of the apoptosis regulators XIAP, XAF1, and Smac/DIABLO in gastric adenocarcinomas. Diagn Mol Pathol. 2007;16:1-8 pubmed
    ..Whereas x-linked inhibitor of apoptosis (XIAP) is a potent inhibitor of apoptosis, its antagonists second mitochondria-derived activator of caspases/direct IAP ..
  86. Shibata T, Noguchi T, Takeno S, Gabbert H, Ramp U, Kawahara K. Disturbed XIAP and XAF1 expression balance is an independent prognostic factor in gastric adenocarcinomas. Ann Surg Oncol. 2008;15:3579-87 pubmed publisher
    Dysregulation of apoptosis is a key factor in carcinogenesis and tumor progression. X-linked inhibitor of apoptosis (XIAP) is the most potent member of the inhibitor of apoptosis protein (IAP) family, which directly inhibits apoptosis by ..
  87. Hu R, Zhu K, Li Y, Yao K, Zhang R, Wang H, et al. Embelin induces apoptosis through down-regulation of XIAP in human leukemia cells. Med Oncol. 2011;28:1584-8 pubmed publisher
    ..Western blot analysis showed that the expression of anti-apoptotic proteins X-linked inhibitor of apoptosis (XIAP) was down-regulated by embelin...
  88. Bartke T, Pohl C, Pyrowolakis G, Jentsch S. Dual role of BRUCE as an antiapoptotic IAP and a chimeric E2/E3 ubiquitin ligase. Mol Cell. 2004;14:801-11 pubmed
    ..Our work suggests that, owing to its two activities and its localization, BRUCE may function as a specialized regulator of cell death pathways. ..
  89. 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 U S A. 2001;98:8662-7 pubmed
    ..One such protein, X-linked IAP (XIAP), inhibits the activity of the cell death proteases, caspase-3, -7, and -9...
  90. Hunter A, Kottachchi D, Lewis J, Duckett C, Korneluk R, Liston P. A novel ubiquitin fusion system bypasses the mitochondria and generates biologically active Smac/DIABLO. J Biol Chem. 2003;278:7494-9 pubmed
    ..The ability to circumvent the requirement for mitochondrial processing and release is critical to developing Smac as a possible gene therapy payload in cancer chemosensitization. ..
  91. Shin H, Okada K, Wilkinson J, Solomon K, Duckett C, Reed J, et al. Identification of ubiquitination sites on the X-linked inhibitor of apoptosis protein. Biochem J. 2003;373:965-71 pubmed
    ..We demonstrate that the auto-ubiquitination sites of the X-linked IAP (XIAP) are Lys(322) and Lys(328), located in the third baculovirus IAP repeat domain of the protein...