BIRC3
Baculoviral IAP repeat-containing protein 3 is a protein in humans that is encoded by BIRC3 gene. Multi-functional protein which regulates not only caspases and apoptosis, but also modulates inflammatory signaling and immunity, mitogenic kinase signaling and cell proliferation, as well as cell invasion and metastasis. Acts as an E3 ubiquitin-protein ligase regulating NF-kappa-B signaling and regulates both canonical and non-canonical NF-kappa-B signaling by acting in opposite directions.
Baculoviral inhibitors of apoptosis repeat-containing protein 3 (BIRC3), also called cellular inhibitors of apoptosis 2 (cIAP2), is a protein in humans that is encoded by BIRC3 gene. The cIAP2 protein contains three BIR domains (BIR1-BIR3), a CARD (caspase-recruitment) domain and a RING (really interesting new gene) zinc-finger domain. The RING domain of cIAP2 possesses E3 ubiquitin ligase activity, which directly regulates auto- or trans-ubiquitination and protein degradation. The BIR1 domains of cIAP2 play a role in tumor necrosis factor (TNF) receptor-associated factor (TRAF) interactions and ubiquitination reactions. Conze DB et al. demonstrated that cIAP1 ubiquitination of cIAP2 leads to low protein levels of cIAP2 in normal conditions by validating cIAP1 E3 ligase function with the cIAP1-null mouse. Increased BIRC3, in combination with BIRC2, acts simultaneously as a positive factor for NF-kappa B signaling, but also as a molecular brake that provides modulatory control over the JNK signaling axis. In the absence of both cIAP1 and cIAP2, TNF alpha-mediated NF- kappa B signaling is dramatically attenuated in many cells, including normal primary cells as well as transformed cancer cells. Consequently, the dual loss of cIAP1 and cIAP2 greatly sensitizes cells to TNF alpha-mediated apoptosis. A recent report also suggests that cIAP1 and cIAP2 promote cancer cell survival by ubiquitinating RIP1, leading to constitutive RIP1 and NF-kappa B activity. High expression of XIAP or cIAP2 is associated with shorter overall survival, and lower complete response rates for AML. |
