BIRC2 Research Reagents

BIRC2 Background

Baculoviral inhibitors of apoptosis repeat-containing protein 2 (BIRC2), also called cellular inhibitors of apoptosis 1 (cIAP1), is a protein in humans that is encoded by BIRC2 gene ^[1][2]. cIAP1 contains three tandem amino-terminal BIR domains, a zinc-binding RING domain at the carboxy terminus, and a caspase-recruitment (CARD) domain in the linker region between the BIR and the RING (Really Interesting New Gene) domains ^[3]. Among the domains of cIAP1, the RING domain exerts an important role in preventing apoptosis. This domain acts as an E3 ligase by binding to E2 ubiquitin-conjugating enzymes (UBCs) and catalyzing the transfer of ubiquitin onto target proteins ^[7] such as caspases, ultimately inhibiting apoptosis ^[3][4]. The CARD domain of cIAP1 is reported to emit a functional nuclear export signal that seems to be important for cell differentiation ^[12]. BIRC2 protein also mediates various cellular functions, including the regulation of signaling and inflammation ^[5]. Rothe M et al. have uncovered that BIRC2 and another IAP family member BIRC3, together with TRAF2, are key components of the TNF signaling pathway that are necessary for TNF-mediated NF-kappa B activation ^[6][7][8]. On the contrary, BIRC2, and BIRC3 act as a molecular brake to rein inactivation of the JNK signaling pathway ^[9]. The amplification and increased levels of cIAP1 have been observed in several cancer types and are required for tumorigenesis in vivo ^[10]. cIAP1 deprivation, caused by IAP antagonist drugs or cIAP1 deletion, might augment physiological TNF-receptor apoptotic signaling, thus resulting in enhanced tumor cell death ^[11]. It suggests a promising cancer treatment by using some IAP antagonist compounds ^[12].

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[2] Rothe M, Pan MG, et al. The TNFR2-TRAF signaling complex contains two novel proteins related to baculoviral inhibitor of apoptosis proteins [J]. Cell. February 1996, 83 (7): 1243-52.
[3] Vaux D.L. & Silke J. IAPs, RINGs and ubiquitylation [J]. Nat. Rev. Mol. Cell Biol. 2005; 6: 287-297.
[4] Lorick, K. L. et al. RING fingers mediate ubiquitin-conjugating enzyme (E2)-dependent ubiquitination [J]. Proc. Natl Acad. Sci. USA 1999, 96, 11364-11369.
[5] Gyrd-Hansen M, Meier P IAPs: from caspase inhibitors to modulators of NF-kappaB, inflammation and cancer [J]. Nat Rev Cancer, 2010, 10:561-574.
[6] Rothe M, Pan MG, et al. The TNFR2-TRAF signaling complex contains two novel proteins related to baculoviral inhibitor of apoptosis proteins [J]. Cell, 1995, 83:1243-1252.
[7] Mahoney DJ, Cheung HH, et al. Both cIAP1 and cIAP2 regulate TNFalpha-mediated NF-kappaB activation [J]. Proc Natl Acad Sci U S A, 2008, 105:11778-11783.
[8] Varfolomeev E, Goncharov T, et al. c-IAP1 and c-IAP2 are critical mediators of tumor necrosis factor alpha (TNFalpha)-induced NF-kappaB activation [J]. J Biol Chem 2008, 283:24295-24299.
[9] B. M. Tan, N. W. Zammit, et al. Baculoviral inhibitors of apoptosis repeat containing (BIRC) proteins fine-tune TNF-induced nuclear factor κB and c-Jun N-terminal kinase signalling in mouse pancreatic beta cells [J]. Diabetologia volume 56, pages520-532 (2013).
[10] Zender L., Spector M.S., et al. Identification and validation of oncogenes in liver cancer using an integrative oncogenomic approach [J]. Cell. 2006; 125: 1253-1267.
[11] James E. Vince, W. Wei-Lynn Wong, et al. IAP Antagonists Target cIAP1 to Induce TNFα-Dependent Apoptosis [J]. VOLUME 131, ISSUE 4, P682-693, NOVEMBER 16, 2007.
[12] Plenchette S, Cathelin S, et al. Translocation of the inhibitor of apoptosis protein c-IAP1 from the nucleus to the Golgi in hematopoietic cells undergoing differentiation: a nuclear export signal-mediated event [J]. Blood, 2004, 104: 2035-2043.