Smac/DIABLO

Background Information:

Smac/DIABLO is a mitochondrial pro-apoptotic protein that functions as a key endogenous antagonist of inhibitor of apoptosis proteins (IAPs). In healthy cells, DIABLO resides in the mitochondrial intermembrane space and, upon apoptotic stimuli, is released into the cytosol where it binds IAPs (e.g. XIAP) via its N-terminal IAP-binding motif, thereby relieving IAP-mediated inhibition of caspases and promoting executioner caspase activation and apoptosis. Beyond its canonical role in apoptosis, studies have uncovered non-apoptotic functions of Smac/DIABLO in cancer biology, including regulation of lipid metabolism and tumor growth, suggesting additional layers of influence on cellular physiology beyond caspase activation. Because dysregulated apoptosis is a hallmark of cancer and therapy resistance, some drug discovery efforts have focused on mimicking the Smac/DIABLO IAP-antagonist function. This has led to the development of small-molecule “Smac mimetics” that replicate Smac/DIABLO’s IAP-binding motif to antagonize IAPs and restore apoptotic responses in cancer cells..

Target Class:

Ubiquitination-related

Family:

Smac/DIABLO

Sub Family:

Regulatory protein

Protein Name:

Smac/DIABLO

Protein Aliases:

SMAC; Smac; DIABLO

Accession Number:

NM_019887.4

UniProt Number:

Q9NR28

Gene Name:

DIABLO

Gene ID:

56616

Gene Aliases:

SMAC; DFNA64

Target Species:

Human