cIAP1, cIAP2, and XIAP

Cellular inhibitor of apoptosis protein 1 (cIAP1), cellular inhibitor of apoptosis protein 2 (cIAP2), and X-linked inhibitor of apoptosis protein (XIAP) are structurally related members of the IAP family. They share conserved baculoviral IAP repeat (BIR) domains required for binding to caspases and, in some cases, direct caspase inhibition (especially XIAP). All contain a RING domain, conferring E3 ubiquitin ligase activity, critical for regulating the stability of themselves and interaction partners. These proteins serve as key regulators at the intersection of apoptosis, immune signaling, and inflammation, playing central roles in cancer cell survival, tumor necrosis factor (TNF) receptor signaling, and innate immunity. Mutations or dysregulation of these proteins is associated with human diseases, especially cancers, and they are actively targeted by novel therapeutics such as Smac mimetics aiming to restore apoptosis in malignant cells.

Other names

BIRC2HIAP2BIRC3HIAP1BIRC4ILP-1

Small-molecule antagonists (Smac mimetics) bind to IAPs, neutralizing their caspase-inhibitory activity or triggering their auto-ubiquitination and proteasomal degradation, thereby reinstating apoptosis in malignant cells.