X-linked IAP is a direct inhibitor of cell-death proteases.
The inhibitor-of-apoptosis (IAP) family of genes has an evolutionarily conserved role in regulating programmed cell death in animals ranging from insects to humans. Ectopic expression of human IAP proteins can suppress cell death induced by a variety of stimuli, but the mechanism of this inhibition was previously unknown. Here we show that human X-chromosome-linked IAP directly inhibits at least two members of the caspase family of cell-death proteases, caspase-3 and caspase-7. As the caspases are highly conserved throughout the animal kingdom and are the principal effectors of apoptosis, our findings suggest how IAPs might inhibit cell death, providing evidence for a mechanism of action for these mammalian cell-death suppressors.
Deveraux
Q L
QL
The Burnham Institute, Program on Apoptosis and Cell Death Research, La Jolla, California 92037, USA.
Takahashi
R
R
Salvesen
G S
GS
Reed
J C
JC
D000595:Amino Acid Sequence; D017209:Apoptosis / Q000502:physiology*; D020170:Caspase 1; D053148:Caspase 3; D053179:Caspase 7; D020169:Caspases; D002467:Cell Nucleus / Q000378:metabolism; D002474:Cell-Free System; D003546:Cysteine Endopeptidases / Q000378:metabolism*; D015853:Cysteine Proteinase Inhibitors / Q000502:physiology*; D003574:Cytochrome c Group / Q000378:metabolism; D003600:Cytosol / Q000378:metabolism; D004789:Enzyme Activation; D008040:Genetic Linkage; D006801:Humans; D019169:Jurkat Cells; D008969:Molecular Sequence Data; D011499:Protein Processing, Post-Translational; D011506:Proteins / Q000235:genetics / Q000502:physiology*; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2; D011994:Recombinant Proteins / Q000378:metabolism; D014162:Transfection; D014960:X Chromosome; D051636:X-Linked Inhibitor of Apoptosis Protein; D051028:bcl-2-Associated X Protein
D015853:Cysteine Proteinase Inhibitors; D003574:Cytochrome c Group; D011506:Proteins; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D011994:Recombinant Proteins; D051636:X-Linked Inhibitor of Apoptosis Protein; C496866:XIAP protein, human; D051028:bcl-2-Associated X Protein; C505407:CASP3 protein, human; C505520:CASP7 protein, human; D053148:Caspase 3; D053179:Caspase 7; D020169:Caspases; D003546:Cysteine Endopeptidases; D020170:Caspase 1