Anti-SMAC/Diablo

Smac/DIABLO (second mitochondrial-derived activator of caspase/direct IAP binding protein with low pI) is encoded by the nucleus and resides as a precursor within the intermembranous space of the mitochondria. During apoptosis, Smac/DIABLO is proteolytically cleaved and released from the mitochondria into the cytosol, where it promotes cell death by interacting with IAPs and inhibiting their anti-apoptotic function. In turn, certain IAPs may degrade Smac/DIABLO and block its cell death function. Smac/DIABLO is expressed in a wide range of normal tissues and some tumor cells lines, and its over-expression in tumor cell lines can trigger both extrinsic and intrinsic apoptosis pathways. Protein function: Promotes apoptosis by activating caspases in the cytochrome c/Apaf-1/caspase-9 pathway. Acts by opposing the inhibitory activity of inhibitor of apoptosis proteins (IAP). Inhibits the activity of BIRC6/bruce by inhibiting its binding to caspases. Isoform 3 attenuates the stability and apoptosis- inhibiting activity of XIAP/BIRC4 by promoting XIAP/BIRC4 ubiquitination and degradation through the ubiquitin-proteasome pathway. Isoform 3 also disrupts XIAP/BIRC4 interacting with processed caspase-9 and promotes caspase-3 activation. Isoform 1 is defective in the capacity to down-regulate the XIAP/BIRC4 abundance. [The UniProt Consortium]