Smac, a mitochondrial protein that promotes cytochrome c-dependent caspase activation by eliminating IAP inhibition.
We report here the identification of a novel protein, Smac, which promotes caspase activation in the cytochrome c/Apaf-1/caspase-9 pathway. Smac promotes caspase-9 activation by binding to inhibitor of apoptosis proteins, IAPs, and removing their inhibitory activity. Smac is normally a mitochondrial protein but is released into the cytosol when cells undergo apoptosis. Mitochondrial import and cleavage of its signal peptide are required for Smac to gain its apoptotic activity. Overexpression of Smac increases cells' sensitivity to apoptotic stimuli. Smac is the second mitochondrial protein, along with cytochrome c, that promotes apoptosis by activating caspases.
Howard Hughes Medical Institute and Department of Biochemistry, University of Texas Southwestern Medical Center at Dallas, 75235, USA.
C
C
Du
M
M
Fang
Y
Y
Li
L
L
Li
X
X
Wang
D000328:Adult; D000595:Amino Acid Sequence; D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins; D053477:Apoptotic Protease-Activating Factor 1; D001483:Base Sequence; D002352:Carrier Proteins; D053148:Caspase 3; D053453:Caspase 9; D020169:Caspases / Q000378:metabolism*; D003001:Cloning, Molecular; D003574:Cytochrome c Group / Q000378:metabolism*; D003600:Cytosol / Q000378:metabolism; D018076:DNA, Complementary; D004789:Enzyme Activation; D004792:Enzyme Precursors / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D008928:Mitochondria / Q000378:metabolism*; D024101:Mitochondrial Proteins; D008969:Molecular Sequence Data; D011499:Protein Processing, Post-Translational; D021382:Protein Sorting Signals / Q000378:metabolism; D011506:Proteins / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D011836:Radiation Tolerance; D014466:Ultraviolet Rays; D051636:X-Linked Inhibitor of Apoptosis Protein
C506592:APAF1 protein, human; D051017:Apoptosis Regulatory Proteins; D053477:Apoptotic Protease-Activating Factor 1; D002352:Carrier Proteins; D003574:Cytochrome c Group; C412403:DIABLO protein, human; D018076:DNA, Complementary; D004792:Enzyme Precursors; D047908:Intracellular Signaling Peptides and Proteins; D024101:Mitochondrial Proteins; D021382:Protein Sorting Signals; D011506:Proteins; D051636:X-Linked Inhibitor of Apoptosis Protein; C496866:XIAP protein, human; C505407:CASP3 protein, human; C506433:CASP9 protein, human; D053148:Caspase 3; D053453:Caspase 9; D020169:Caspases