cIAP

Cellular inhibitors of apoptosis proteins (cIAPs), including cIAP1 and cIAP2, function as E3 ubiquitin ligases that regulate apoptosis, innate immune signaling, and NF-κB activation^[1][2]. Mechanistically, cIAP1 promotes NF-κB-dependent gene expression in skeletal muscle, contributing to denervation-induced atrophy, whereas cIAP2 modulates inflammasome activation and intestinal epithelial regeneration^[3][4]. cIAP1 and cIAP2 also mediate NOD1/NOD2 receptor signaling through RIP2 ubiquitination, critical for cytokine production and host defense against inflammatory insults^[5]. Compared with other IAP isoforms such as XIAP, cIAP1/2 exhibit isoform-specific roles in regulating Ripoptosome assembly, with cIAP absence promoting RIP1/caspase-8 complex formation that determines apoptotic or necroptotic outcomes^[6]. In disease models, cIAP1 and cIAP2 overexpression supports tumorigenesis by sustaining NF-κB signaling, whereas their inhibition can sensitize cancer or proinflammatory macrophages to apoptosis^[7][8][9]. Agonists or small-molecule IAP antagonists, including SMAC mimetics, selectively degrade cIAP1/2, enhancing death receptor-mediated apoptosis and reducing pathogenic cell survival, demonstrating their utility as experimental tools and therapeutic candidates^[9][10]. Therefore, cIAPs act at the intersection of apoptosis, immune signaling, and disease modulation, with isoform-specific mechanisms providing a foundation for targeted intervention in cancer, inflammatory diseases, and tissue regeneration^[1][2].

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