Cellular inhibitor of apoptosis protein 1 (cIAP1) BIR2 domain (cIAP1 BIR2)

The Cellular inhibitor of apoptosis protein 1 (cIAP1) BIR2 domain is a critical structural motif within the BIRC2 protein that plays a pivotal role in regulating programmed cell death and inflammatory signaling (Source: UniProt P98170). As a member of the IAP family, cIAP1 contains three Baculovirus IAP Repeat (BIR) domains, with the BIR2 domain specifically involved in the inhibition of effector caspases, such as Caspase-3 and Caspase-7, and the regulation of the canonical NF-kappaB pathway (Source: PubMed PMID: 18463613). In many cancers, cIAP1 is overexpressed, leading to evasion of apoptosis and resistance to chemotherapy. Therapeutic strategies targeting this domain primarily involve SMAC mimetics, which are small molecules designed to mimic the endogenous pro-apoptotic protein SMAC/DIABLO (Source: PubMed PMID: 28211549). These drugs bind to the BIR2 and BIR3 domains, inducing conformational changes that trigger cIAP1 autoubiquitination and degradation, thereby restoring apoptotic sensitivity in malignant cells. Consequently, the cIAP1 BIR2 domain is a significant focal point for developing novel oncology treatments aimed at overcoming cell death resistance.

Other names

Baculoviral IAP repeat-containing protein 2 BIR2 domainBIRC2 BIR2HIAP2 BIR2MIHB BIR2Mammalian IAP homolog B BIR2IAP-C BIR2

SMAC mimetics bind to the BIR2 and BIR3 domains of cIAP1, mimicking the endogenous IAP antagonist SMAC/DIABLO. This binding triggers the E3 ubiquitin ligase activity of cIAP1, leading to its rapid autoubiquitination and proteasomal degradation, which subsequently promotes TNF-alpha-mediated apoptosis and sensitizes tumor cells to death stimuli (Source: PubMed PMID: 24469444, UniProt P98170).