Nuclear Apaf-1 and cytochrome c redistribution following stress-induced apoptosis.
Apoptotic protease activating factor-1 (Apaf-1) and cytochrome c are cofactors critical for inducing caspase-9 activation following stress-induced apoptosis. One consequence of caspase-9 activation is nuclear-cytoplasmic barrier disassembly, which is required for nuclear caspase-3 translocation. In the nucleus, caspase-3 triggers proteolysis of the caspase-activated DNA nuclease (CAD) inhibitor, causing CAD induction and subsequent DNA degradation. Here we demonstrate that apoptotic cells show perinuclear cytochrome c aggregation, which may be critical for nuclear redistribution of cytochrome c and Apaf-1. We thus indicate that the nuclear redistribution of these cofactors concurs with the previously reported caspase-9-induced nuclear disassembly, and may represent an early apoptotic hallmark.
Ruiz-Vela
Antonio
A
Department of Immunology and Oncology, Centro Nacional de Biotecnología/CSIC, Universidad Autónoma de Madrid, Campus de Cantoblanco, Madrid, Spain. aruiz@cnb.uam.es
González de Buitrago
Gonzalo
G
Martínez-A
Carlos
C
D016475:3T3 Cells / Q000378:metabolism; D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D053477:Apoptotic Protease-Activating Factor 1; D053453:Caspase 9; D020169:Caspases / Q000378:metabolism*; D002467:Cell Nucleus / Q000378:metabolism*; D003574:Cytochrome c Group / Q000378:metabolism*; D004789:Enzyme Activation; D006367:HeLa Cells / Q000378:metabolism; D006801:Humans; D051379:Mice; D021381:Protein Transport; D011506:Proteins / Q000378:metabolism*
C506592:APAF1 protein, human; C506593:Apaf1 protein, mouse; D053477:Apoptotic Protease-Activating Factor 1; D003574:Cytochrome c Group; D011506:Proteins; C506433:CASP9 protein, human; C506434:Casp9 protein, mouse; D053453:Caspase 9; D020169:Caspases