Caspase-9, Bcl-XL, and Apaf-1 form a ternary complex.
Genetic analysis of apoptosis in the nematode Caenorhabditis elegans has revealed the cell death machine to be composed of three core interacting components. CED-4 (equivalent to mammalian Apaf-1) is a nucleotide binding molecule that complexes with the zymogen form of the death protease CED-3, leading to its autoactivation and cell death. CED-9 blocks death by complexing with CED-4 and attenuating its ability to promote CED-3 activation. An equivalent ternary complex was found to be present in mammalian cells involving Apaf-1, the mammalian death protease caspase-9, and Bcl-XL, an anti-apoptotic member of the Bcl-2 family. Consistent with a central role for caspase-9, a dominant negative form effectively inhibited cell death initiated by a wide variety of inducers.
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Department of Pathology, University of Michigan Medical School, Ann Arbor, Michigan 48109, USA.
O'Rourke
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Dixit
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D000906:Antibodies / Q000276:immunology / Q000494:pharmacology; D017209:Apoptosis / Q000502:physiology*; D051017:Apoptosis Regulatory Proteins; D053477:Apoptotic Protease-Activating Factor 1; D001943:Breast Neoplasms / Q000378:metabolism; D053453:Caspase 9; D020169:Caspases; D003546:Cysteine Endopeptidases / Q000502:physiology*; D005260:Female; D015870:Gene Expression / Q000235:genetics; D017930:Genes, Reporter / Q000235:genetics; D006801:Humans; D008562:Membrane Glycoproteins / Q000502:physiology; D008565:Membrane Proteins / Q000502:physiology; D024101:Mitochondrial Proteins; D011485:Protein Binding / Q000502:physiology; D011487:Protein Conformation; D011506:Proteins / Q000502:physiology; D011518:Proto-Oncogene Proteins / Q000502:physiology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000502:physiology*; D053221:TNF-Related Apoptosis-Inducing Ligand; D014162:Transfection / Q000235:genetics; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology; D050998:bcl-2 Homologous Antagonist-Killer Protein; D051028:bcl-2-Associated X Protein; D051020:bcl-X Protein; D019014:fas Receptor / Q000276:immunology / Q000502:physiology
C506592:APAF1 protein, human; D000906:Antibodies; D051017:Apoptosis Regulatory Proteins; D053477:Apoptotic Protease-Activating Factor 1; C494772:BAK1 protein, human; C494811:BCL2L1 protein, human; C096820:BIK protein, human; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D024101:Mitochondrial Proteins; D011506:Proteins; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D053221:TNF-Related Apoptosis-Inducing Ligand; C505653:TNFSF10 protein, human; D014409:Tumor Necrosis Factor-alpha; D050998:bcl-2 Homologous Antagonist-Killer Protein; D051028:bcl-2-Associated X Protein; D051020:bcl-X Protein; D019014:fas Receptor; C506433:CASP9 protein, human; D053453:Caspase 9; D020169:Caspases; D003546:Cysteine Endopeptidases