BIRC6 (Baculoviral IAP repeat-containing 6)

The BIRC6 gene (BRUCE/APOLLON) encodes the cytoplasmic protein BIRC6 in mammals, consisting of a single N-terminal baculoviral IAP repeat (BIR) domain and a C-terminal ubiquitin-conjugating (UBC) domain. Of the huge protein size at 528 kDa, BIRC6 demonstrated pleiotropic functions including inhibition of apoptosis, cytoprotection, regulation of cytokinesis, mitosis, autophagy and neutrophil differentiation. With the BIR domain, BIRC6 is defined as a member of the Inhibitor of Apoptosis (IAP) family. Through its BIR domain, BIRC6 binds to active caspases, including caspases-3, 6, 7 and 9 and accounts for its ability to inhibit the caspase cascade and ultimately apoptosis. The UBC domain has chimeric E2/E3 ubiquitin ligase activity where it facilitates proteosomal degradation of various proteins, including pro-apoptotic proteins p53, caspases, Smac and mitotic regulator cyclin A. More importantly, the UBC domain plays an indispensable role in embryonic development in mammals and spermatogenesis in Drosophila. Increasing evidence supports the cancer promoting role of BIRC6. Elevated BIRC6 expression has been found in a variety of cancers and was shown to contribute to treatment resistance