Baculoviral IAP repeat-containing protein 3 (cIAP-2) (cIAP-2)

Baculoviral IAP repeat-containing protein 3 (cIAP-2) is a multifunctional E3 ubiquitin-protein ligase and a member of the inhibitor of apoptosis (IAP) family. It serves as a critical regulator of cell survival, inflammation, and innate immunity by modulating signaling pathways such as NF-kappaB and TNF receptor signaling [3, 11]. In oncology, cIAP-2 is frequently overexpressed or involved in genetic translocations, such as the cIAP2-MALT1 fusion, which promotes tumor cell resistance to apoptosis and contributes to the pathogenesis of MALT lymphomas [17]. Therapeutic targeting of cIAP-2 is primarily achieved through SMAC mimetics, which are small molecules that mimic the endogenous IAP antagonist SMAC/DIABLO [1, 15]. These drugs bind to the BIR domains of cIAP-2, triggering its autoubiquitination and rapid proteasomal degradation, thereby sensitizing cancer cells to pro-apoptotic stimuli [6, 14]. Clinical development of these inhibitors has highlighted their potential in combination therapies, although challenges such as cytokine release syndrome and off-target inflammatory effects remain [11, 19].

Other names

BIRC3API2HIAP1MIHCRNF49HAIP1

SMAC mimetics bind to the BIR3 domain of cIAP-2, inducing its autoubiquitination and proteasomal degradation, which sensitizes cells to apoptosis and activates non-canonical NF-kappaB signaling.