Baculoviral IAP repeat-containing protein (BIRC)

Baculoviral IAP repeat-containing proteins (BIRC) are a family of apoptosis inhibitors characterized by the presence of one or more baculoviral IAP repeat (BIR) domains and often a C-terminal RING finger domain[1][2][3]. They function by directly binding and inhibiting caspases, the central effectors of apoptosis, thereby preventing cell death[3]. BIRC proteins also act as E3 ubiquitin ligases, targeting various proteins, including themselves, for ubiquitination and subsequent proteasomal degradation[3][2]. These proteins regulate not only cell death but also inflammatory pathways by interacting with signaling molecules like TRAF1 and TRAF2[2][3]. Dysregulated BIRC/IAP family members have been implicated in cancer, particularly in promoting tumor cell survival, resistance to apoptosis, and treatment resistance[3][2][4]. Small molecule SMAC mimetics have been developed to antagonize IAP activity, representing a therapeutic strategy in oncology[3]. The family includes several human proteins such as XIAP (BIRC4), c-IAP1 (BIRC2), c-IAP2 (BIRC3), NAIP (BIRC1), survivin (BIRC5), and others, all playing varied roles in cell biology, immunity, and disease[3][4][7].

Other names

Inhibitor of apoptosis proteinIAPBIRC family (e.g. BIRC1/NAIP, BIRC2/c-IAP1, BIRC3/c-IAP2, BIRC4/XIAP, BIRC5/Survivin, BIRC6/Apollon, BIRC7/Livin, BIRC8/IAP-like protein 2)

Antagonism of IAP-caspase interaction leading to caspase activation and apoptosis; Promotion of c-IAP1 and c-IAP2 autoubiquitination and proteasomal degradation; Disruption of IAP-mediated pro-survival signaling