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Gene Review

BIRC3  -  baculoviral IAP repeat containing 3

Homo sapiens

Synonyms: AIP1, API2, Apoptosis inhibitor 2, Baculoviral IAP repeat-containing protein 3, C-IAP2, ...
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Disease relevance of BIRC3


Psychiatry related information on BIRC3


High impact information on BIRC3


Chemical compound and disease context of BIRC3


Biological context of BIRC3


Anatomical context of BIRC3


Associations of BIRC3 with chemical compounds

  • Cinnamaldehyde also upregulated the expression of pro-apoptotic protein (Bax) and down-regulated the levels of anti-apoptotic proteins, such as Bcl-2 and the inhibitor of apoptosis protein family (X-linked inhibitor of apoptosis protein (XIAP), cellular inhibitor of apoptosis protein (cIAP)-1 and cIAP-2) [21].
  • The use of leptomycin B, an NES-specific inhibitor, demonstrated that both MALT1 and API2-MALT1 were predominantly retained in the nuclei, indicating that these molecules were shuttling between nucleus and cytoplasm in an NES-dependent manner [22].
  • Transcription of cIAP-2 and XIAP was up-regulated by the phosphatidylinositol 3-kinase/Akt pathway as shown by its reversal by dominant-negative Akt or LY294002 [23].
  • The ubiquitin E3 ligase activity is inhibited by cysteine-alkylating reagents, supported by E2UBCH7, and requires cIAP2 or a cIAP2-associated protein for activity [24].
  • Dynamic subcellular localization is an important regulatory mechanism for many proteins. cIAP1 and cIAP2 are two closely related members of inhibitor of apoptosis (IAP) family that play a role both as caspase inhibitors and as mediators of tumor necrosis factor (TNF) receptor signaling [25].
  • To test the involvement of cIAP2 on cisplatin resistance, IC(50) was lowered to 8.6 μmol/L in TL-1 cells with cIAP2 short hairpin RNA (shRNA) transfection and compared with 39.7 μmol/L in TL-1 cells with nonspecific shRNA [26].

Regulatory relationships of BIRC3

  • Among these members, cIAP2 expression was selectively up-regulated by stimulation with granulocyte colony-stimulating factor (G-CSF), but not with granulocyte-macrophage CSF [2].
  • Two of the inhibitor-of-apoptosis proteins were downregulated because of an increase in 'second mitochondrial activator of caspases/Direct inhibitor-of-apoptosis protein binding protein with low pI.' Decrease in nuclear factor kappa B and increase in inhibitor of nuclear factor kappa B alpha expression favored the process of apoptosis [27].
  • API2-MALT1 fusion protein induces transcriptional activation of the API2 gene through NF-kappaB binding elements: evidence for a positive feed-back loop pathway resulting in unremitting NF-kappaB activation [28].
  • These findings demonstrate that BRF1 expression enhanced cisplatin sensitivity in HNSCC cells by reducing the levels of cIAP2 mRNA [29].
  • Our data suggest that AFP may regulate cell death by displacing cIAP-2 from the apoptosome, resulting in promotion of caspase 3 activation and its release from the complex [30].

Other interactions of BIRC3

  • The c-IAP-1 and c-IAP-2 proteins are direct inhibitors of specific caspases [31].
  • These data suggest a novel mechanism for the anti-apoptotic function mediated by the PKC delta/NF-kappa B/cIAP-2 pathway in certain cancers [4].
  • Human tumours were linked to clinical data and it was found that IAP-1 and survivin mRNA expression patterns were associated with a relatively shorter patient survival, while those of XIAP and livin were associated with a relatively longer patient survival [10].
  • We describe the synthesis and properties of a small molecule mimic of Smac, a pro-apoptotic protein that functions by relieving inhibitor-of-apoptosis protein (IAP)-mediated suppression of caspase activity [32].
  • The suppression of NFkappaB activation correlated with sequential inhibition of the tumor necrosis factor-induced expression of NFkappaB-regulated anti-apoptotic (IAP1, IAP2, Bcl-2, Bcl-xL, cFLIP, Bfl-1/A1, and survivin) gene products [33].

Analytical, diagnostic and therapeutic context of BIRC3


  1. NMR structure and mutagenesis of the inhibitor-of-apoptosis protein XIAP. Sun, C., Cai, M., Gunasekera, A.H., Meadows, R.P., Wang, H., Chen, J., Zhang, H., Wu, W., Xu, N., Ng, S.C., Fesik, S.W. Nature (1999) [Pubmed]
  2. Expression of the inhibitor of apoptosis (IAP) family members in human neutrophils: up-regulation of cIAP2 by granulocyte colony-stimulating factor and overexpression of cIAP2 in chronic neutrophilic leukemia. Hasegawa, T., Suzuki, K., Sakamoto, C., Ohta, K., Nishiki, S., Hino, M., Tatsumi, N., Kitagawa, S. Blood (2003) [Pubmed]
  3. Antiapoptotic function of apoptosis inhibitor 2-MALT1 fusion protein involved in t(11;18)(q21;q21) mucosa-associated lymphoid tissue lymphoma. Hosokawa, Y., Suzuki, H., Suzuki, Y., Takahashi, R., Seto, M. Cancer Res. (2004) [Pubmed]
  4. Induction of cIAP-2 in human colon cancer cells through PKC delta/NF-kappa B. Wang, Q., Wang, X., Evers, B.M. J. Biol. Chem. (2003) [Pubmed]
  5. Differential regulation of inhibitors of apoptosis proteins in Alzheimer's disease brains. Christie, L.A., Su, J.H., Tu, C.H., Dick, M.C., Zhou, J., Cotman, C.W. Neurobiol. Dis. (2007) [Pubmed]
  6. The TNFR2-TRAF signaling complex contains two novel proteins related to baculoviral inhibitor of apoptosis proteins. Rothe, M., Pan, M.G., Henzel, W.J., Ayres, T.M., Goeddel, D.V. Cell (1995) [Pubmed]
  7. NF-kappaB antiapoptosis: induction of TRAF1 and TRAF2 and c-IAP1 and c-IAP2 to suppress caspase-8 activation. Wang, C.Y., Mayo, M.W., Korneluk, R.G., Goeddel, D.V., Baldwin, A.S. Science (1998) [Pubmed]
  8. Omi/HtrA2 catalytic cleavage of inhibitor of apoptosis (IAP) irreversibly inactivates IAPs and facilitates caspase activity in apoptosis. Yang, Q.H., Church-Hajduk, R., Ren, J., Newton, M.L., Du, C. Genes Dev. (2003) [Pubmed]
  9. Granzyme B-induced apoptosis requires both direct caspase activation and relief of caspase inhibition. Goping, I.S., Barry, M., Liston, P., Sawchuk, T., Constantinescu, G., Michalak, K.M., Shostak, I., Roberts, D.L., Hunter, A.M., Korneluk, R., Bleackley, R.C. Immunity (2003) [Pubmed]
  10. Expression patterns of inhibitor of apoptosis proteins in malignant pleural mesothelioma. Gordon, G.J., Mani, M., Mukhopadhyay, L., Dong, L., Edenfield, H.R., Glickman, J.N., Yeap, B.Y., Sugarbaker, D.J., Bueno, R. J. Pathol. (2007) [Pubmed]
  11. API2-MALT1 fusion defines a distinctive clinicopathologic subtype in pulmonary extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue. Okabe, M., Inagaki, H., Ohshima, K., Yoshino, T., Li, C., Eimoto, T., Ueda, R., Nakamura, S. Am. J. Pathol. (2003) [Pubmed]
  12. What doesn't kill you makes you stronger: how hepatocytes survive prolonged cholestasis. Maher, J.J. Hepatology (2004) [Pubmed]
  13. Glucocorticoids inhibit cell death in ovarian cancer and up-regulate caspase inhibitor cIAP2. Runnebaum, I.B., Brüning, A. Clin. Cancer Res. (2005) [Pubmed]
  14. Inhibitor of apoptosis-1 (IAP-1) expression and apoptosis in non-small-cell lung cancer cells exposed to gemcitabine. Bandala, E., Espinosa, M., Maldonado, V., Meléndez-Zajgla, J. Biochem. Pharmacol. (2001) [Pubmed]
  15. Expression and biological activity of X-linked inhibitor of apoptosis (XIAP) in human malignant glioma. Wagenknecht, B., Glaser, T., Naumann, U., Kügler, S., Isenmann, S., Bähr, M., Korneluk, R., Liston, P., Weller, M. Cell Death Differ. (1999) [Pubmed]
  16. Detection of t(11;18)(q21;q21) by interphase fluorescence in situ hybridization using API2 and MLT specific probes. Dierlamm, J., Baens, M., Stefanova-Ouzounova, M., Hinz, K., Wlodarska, I., Maes, B., Steyls, A., Driessen, A., Verhoef, G., Gaulard, P., Hagemeijer, A., Hossfeld, D.K., De Wolf-Peeters, C., Marynen, P. Blood (2000) [Pubmed]
  17. Bcl-2 and Bcl-xL inhibit CD95-mediated apoptosis by preventing mitochondrial release of Smac/DIABLO and subsequent inactivation of X-linked inhibitor-of-apoptosis protein. Sun, X.M., Bratton, S.B., Butterworth, M., MacFarlane, M., Cohen, G.M. J. Biol. Chem. (2002) [Pubmed]
  18. Vascular endothelial genes that are responsive to tumor necrosis factor-alpha in vitro are expressed in atherosclerotic lesions, including inhibitor of apoptosis protein-1, stannin, and two novel genes. Horrevoets, A.J., Fontijn, R.D., van Zonneveld, A.J., de Vries, C.J., ten Cate, J.W., Pannekoek, H. Blood (1999) [Pubmed]
  19. Chenodeoxycholic acid and taurochenodexycholic acid induce anti-apoptotic cIAP-1 expression in human hepatocytes. Hirano, F., Haneda, M., Makino, I. J. Gastroenterol. Hepatol. (2006) [Pubmed]
  20. Anti-apoptotic role of focal adhesion kinase (FAK). Induction of inhibitor-of-apoptosis proteins and apoptosis suppression by the overexpression of FAK in a human leukemic cell line, HL-60. Sonoda, Y., Matsumoto, Y., Funakoshi, M., Yamamoto, D., Hanks, S.K., Kasahara, T. J. Biol. Chem. (2000) [Pubmed]
  21. Effects of vitamin E on the cinnamaldehyde-induced apoptotic mechanism in human PLC/PRF/5 cells. Wu, S.J., Ng, L.T., Lin, C.C. Clin. Exp. Pharmacol. Physiol. (2004) [Pubmed]
  22. MALT1 contains nuclear export signals and regulates cytoplasmic localization of BCL10. Nakagawa, M., Hosokawa, Y., Yonezumi, M., Izumiyama, K., Suzuki, R., Tsuzuki, S., Asaka, M., Seto, M. Blood (2005) [Pubmed]
  23. Critical role of endogenous Akt/IAPs and MEK1/ERK pathways in counteracting endoplasmic reticulum stress-induced cell death. Hu, P., Han, Z., Couvillon, A.D., Exton, J.H. J. Biol. Chem. (2004) [Pubmed]
  24. A small molecule ubiquitination inhibitor blocks NF-kappa B-dependent cytokine expression in cells and rats. Swinney, D.C., Xu, Y.Z., Scarafia, L.E., Lee, I., Mak, A.Y., Gan, Q.F., Ramesha, C.S., Mulkins, M.A., Dunn, J., So, O.Y., Biegel, T., Dinh, M., Volkel, P., Barnett, J., Dalrymple, S.A., Lee, S., Huber, M. J. Biol. Chem. (2002) [Pubmed]
  25. Nuclear shuttling and TRAF2-mediated retention in the cytoplasm regulate the subcellular localization of cIAP1 and cIAP2. Vischioni, B., Giaccone, G., Span, S.W., Kruyt, F.A., Rodriguez, J.A. Exp. Cell Res. (2004) [Pubmed]
  26. cIAP2 upregulated by E6 oncoprotein via epidermal growth factor receptor/phosphatidylinositol 3-kinase/AKT pathway confers resistance to cisplatin in human papillomavirus 16/18-infected lung cancer. Wu, H.H., Wu, J.Y., Cheng, Y.W., Chen, C.Y., Lee, M.C., Goan, Y.G., Lee, H. Clin. Cancer Res. (2010) [Pubmed]
  27. Activation of multiple molecular mechanisms for apoptosis in human malignant glioblastoma T98G and U87MG cells treated with sulforaphane. Karmakar, S., Weinberg, M.S., Banik, N.L., Patel, S.J., Ray, S.K. Neuroscience (2006) [Pubmed]
  28. API2-MALT1 fusion protein induces transcriptional activation of the API2 gene through NF-kappaB binding elements: evidence for a positive feed-back loop pathway resulting in unremitting NF-kappaB activation. Hosokawa, Y., Suzuki, H., Nakagawa, M., Lee, T.H., Seto, M. Biochem. Biophys. Res. Commun. (2005) [Pubmed]
  29. Butyrate response factor 1 enhances cisplatin sensitivity in human head and neck squamous cell carcinoma cell lines. Lee, S.K., Kim, S.B., Kim, J.S., Moon, C.H., Han, M.S., Lee, B.J., Chung, D.K., Min, Y.J., Park, J.H., Choi, D.H., Cho, H.R., Park, S.K., Park, J.W. Int. J. Cancer (2005) [Pubmed]
  30. Alpha-fetoprotein positively regulates cytochrome c-mediated caspase activation and apoptosome complex formation. Semenkova, L., Dudich, E., Dudich, I., Tokhtamisheva, N., Tatulov, E., Okruzhnov, Y., Garcia-Foncillas, J., Palop-Cubillo, J.A., Korpela, T. Eur. J. Biochem. (2003) [Pubmed]
  31. The c-IAP-1 and c-IAP-2 proteins are direct inhibitors of specific caspases. Roy, N., Deveraux, Q.L., Takahashi, R., Salvesen, G.S., Reed, J.C. EMBO J. (1997) [Pubmed]
  32. A small molecule Smac mimic potentiates TRAIL- and TNFalpha-mediated cell death. Li, L., Thomas, R.M., Suzuki, H., De Brabander, J.K., Wang, X., Harran, P.G. Science (2004) [Pubmed]
  33. PTEN enhances TNF-induced apoptosis through modulation of nuclear factor-kappaB signaling pathway in human glioma cells. Koul, D., Takada, Y., Shen, R., Aggarwal, B.B., Yung, W.K. Biochem. Biophys. Res. Commun. (2006) [Pubmed]
  34. A role of inhibitor of apoptosis (IAP) proteins in increased lymphocyte apoptosis in aged humans. Gupta, S. Mech. Ageing Dev. (2004) [Pubmed]
  35. The product of the t(11;18), an API2-MLT fusion, marks nearly half of gastric MALT type lymphomas without large cell proliferation. Baens, M., Maes, B., Steyls, A., Geboes, K., Marynen, P., De Wolf-Peeters, C. Am. J. Pathol. (2000) [Pubmed]
  36. Protective roles of NF-kappa B for chromium(VI)-induced cytotoxicity is revealed by expression of Ikappa B kinase-beta mutant. Chen, F., Bower, J., Leonard, S.S., Ding, M., Lu, Y., Rojanasakul, Y., Kung, H.F., Vallyathan, V., Castranova, V., Shi, X. J. Biol. Chem. (2002) [Pubmed]
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