Apaf-1, a human protein homologous to C. elegans CED-4, participates in cytochrome c-dependent activation of caspase-3.
We report here the purification and cDNA cloning of Apaf-1, a novel 130 kd protein from HeLa cell cytosol that participates in the cytochrome c-dependent activation of caspase-3. The NH2-terminal 85 amino acids of Apaf-1 show 21% identity and 53% similarity to the NH2-terminal prodomain of the Caenorhabditis elegans caspase, CED-3. This is followed by 320 amino acids that show 22% identity and 48% similarity to CED-4, a protein that is believed to initiate apoptosis in C. elegans. The COOH-terminal region of Apaf-1 comprises multiple WD repeats, which are proposed to mediate protein-protein interactions. Cytochrome c binds to Apaf-1, an event that may trigger the activation of caspase-3, leading to apoptosis.
Zou
H
H
Department of Biochemistry, University of Texas Southwestern Medical Center at Dallas, 75235, USA.
Henzel
W J
WJ
Liu
X
X
Lutschg
A
A
Wang
X
X
D000595:Amino Acid Sequence; D000818:Animals; D053477:Apoptotic Protease-Activating Factor 1; D017173:Caenorhabditis elegans / Q000378:metabolism; D029742:Caenorhabditis elegans Proteins; D002135:Calcium-Binding Proteins / Q000378:metabolism; D053148:Caspase 3; D020169:Caspases; D002460:Cell Line; D003001:Cloning, Molecular; D003546:Cysteine Endopeptidases / Q000096:biosynthesis / Q000378:metabolism*; D003574:Cytochrome c Group / Q000378:metabolism*; D003600:Cytosol / Q000378:metabolism; D018076:DNA, Complementary; D004789:Enzyme Activation; D004792:Enzyme Precursors / Q000378:metabolism; D006367:HeLa Cells; D015801:Helminth Proteins / Q000378:metabolism; D006801:Humans; D008969:Molecular Sequence Data; D011506:Proteins / Q000737:chemistry* / Q000302:isolation & purification / Q000378:metabolism*; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D014162:Transfection
C506592:APAF1 protein, human; D053477:Apoptotic Protease-Activating Factor 1; D029742:Caenorhabditis elegans Proteins; D002135:Calcium-Binding Proteins; C089224:Ced-4 protein, C elegans; D003574:Cytochrome c Group; D018076:DNA, Complementary; D004792:Enzyme Precursors; D015801:Helminth Proteins; D011506:Proteins; D011994:Recombinant Proteins; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases; D003546:Cysteine Endopeptidases