c-IAP1 (F7C3U) Rabbit mAb #96099

The inhibitor of apoptosis protein (IAP) family consists of an evolutionarily conserved group of apoptosis inhibitors containing a conserved 70 amino acid BIR (baculovirus inhibitor repeat) domain (1,2). Human members of this family include c-IAP1, c-IAP2, XIAP, survivin, livin, and NAIP. Overexpression of IAP family members, particularly survivin and livin, in cancer cell lines and primary tumors suggests an important role for these proteins in cancer progression (3-5). In general, the IAP proteins function through direct interactions to inhibit the activity of several caspases, including caspase-3, caspase-7, and caspase-9 (5,6). In addition, binding of IAP family members to the mitochondrial protein Smac blocks their interaction with caspase-9, thereby allowing the processing and activation of the caspase (2).

c-IAP1 (gene name: BIRC2), which is structurally and functionally closely related to c-IAP2 (gene name: BIRC3), also contains a RING domain that confers E3 ubiquitin ligase activity (7). c-IAP1 is recruited to the TNF receptor complex upon ligand binding and functions as a positive regulator of the canonical NF-κB signaling pathway, leading to autoubiquitination as well as ubiquitination of other signaling targets, including RIP1 and TRAF family members (8-11). c-IAP is frequently overexpressed in many cancers, contributing to tumorigenesis by inhibiting apoptosis (12,13). IAP inhibitors, like Smac mimetics, can result in c-IAP1 degradation and have been pursued as therapeutic opportunities (14).