Diablo homolog, mitochondrial (DIABLO)

Diablo homolog, mitochondrial (DIABLO/SMAC) is a mitochondrial protein crucial for regulating apoptosis. Upon receipt of apoptotic signals and following mitochondrial outer membrane permeabilization, DIABLO/SMAC is released from the mitochondria into the cytosol, where it binds and neutralizes inhibitor of apoptosis proteins (IAPs) such as XIAP and cIAPs. This inhibition releases the suppression of caspases, thereby promoting apoptotic cell death. Structurally, DIABLO/SMAC is processed inside mitochondria to expose an N-terminal AVPI tetrapeptide crucial for IAP binding. DIABLO/SMAC plays a key role in regulating cell death and is implicated in diseases where apoptosis is disrupted, such as cancer and neurodegeneration. Because of its role in overcoming cellular apoptosis resistance, DIABLO/SMAC and its pathway are considered therapeutic targets, and small-molecule SMAC mimetics have been developed as cancer therapies to restore apoptosis in tumor cells

Other names

DIABLOSMACsecond mitochondria-derived activator of caspasesdirect IAP-binding protein with low pIDFNA64diablo-like proteinDIABLO-SFLJ25049FLJ10537

Antagonism of inhibitor of apoptosis proteins (IAP) to promote caspase activation and apoptosis. Sensitization of tumor cells to chemotherapy/irradiation-induced cell death by freeing caspases from IAP inhibition