cIAP1

Cellular inhibitor of apoptosis protein 1 (cIAP1) is a multifunctional E3 ubiquitin ligase that regulates apoptosis, NF-κB signaling, and cell proliferation in both cytoplasmic and nuclear compartments^[1][4]. Mechanistically, cIAP1 modulates tumor necrosis factor receptor (TNFR) and pattern recognition receptor (PRR) signaling, thereby influencing innate immunity, inflammasome activation, and transcriptional control via E2F1^[1][4][5][6]. Compared with cIAP2, cIAP1 exhibits distinct nuclear functions, including direct binding to E2F1 and enhancement of CCNE and CCNA gene transcription, which promotes cell cycle progression^[4]. In disease models, cIAP1 contributes to tumor growth through interactions with TRAF2, activating the canonical NF-κB and JAK/STAT3 pathways, and sustaining survival in gallbladder cancer, non-small cell lung cancer, and skeletal muscle atrophy models^{[12][6][2][7]}. Furthermore, cIAP1 is required for T cell costimulation through CD137 signaling, mediating NF-κB and MAPK activation, which is critical for antitumor immune responses^[3]. Pharmacologically, cIAP1 degradation by SMAC mimetics or selective inhibitors potentiates apoptosis by releasing RIP1 and activating caspase complexes, highlighting its potential as a therapeutic target in cancer and immune-related diseases^[8][3]. Overall, the unique nuclear and cytoplasmic functions of cIAP1 distinguish it from cIAP2, enabling diverse applications in experimental oncology, immunology, and tissue regeneration studies.