IAP

IAPs (inhibitor of apoptosis proteins) regulate cell death and survival through BIR-domain interactions and RING-dependent ubiquitin ligase activity^[1]. Mechanistically, cIAP1 and cIAP2 act as direct E3 ubiquitin ligases for RIP1-4, supporting RIP-dependent NF-κB signaling^[2]. In cancer models, cIAP2-mediated K63 ubiquitination of RIP1 maintains pro-survival signaling, whereas IAP BIR antagonists remove this ubiquitination and promote caspase-8-dependent death^[3]. Compared with cIAP1/2, XIAP more directly inhibits caspase-3, caspase-7, and caspase-9, which distinguishes XIAP-centered apoptosis control from cIAP-centered receptor signaling^[3]. For experimental applications, Smac mimetics bind IAP BIR domains, induce proteasomal degradation of cIAP1/2, stabilize NIK, and activate noncanonical NF-κB signaling^[4][5]. In targeted protein degradation, SNIPERs recruit IAP ubiquitin ligases to degrade disease-associated proteins, including ERα in breast tumor xenograft models^[6][7].