Formation of apoptosome is initiated by cytochrome c -induced dATP hydrolysis and subsequent nucleotide exchange on Apaf-1
- 26 October 2005
- journal article
- Published by Proceedings of the National Academy of Sciences in Proceedings of the National Academy of Sciences of the United States of America
- Vol. 102 (49), 17545-17550
- https://doi.org/10.1073/pnas.0507900102
Abstract
Apoptosis in metazoans is executed by a group of intracellular proteases named caspases. One of the caspase-activating pathways in mammals is initiated by the release of cytochrome c from mitochondria to cytosol, where it binds to Apaf-1 to form a procaspase-9-activating heptameric protein complex named apoptosome. We report here the reconstitution of this pathway with purified recombinant Apaf-1, procaspase-9, procaspase-3, and cytochrome c from horse heart. Apaf-1 contains a dATP as a cofactor. Cytochrome c binding to Apaf-1 induces hydrolysis of dATP to dADP, which is subsequently replaced by exogenous dATP. The dATP hydrolysis and exchange on Apaf-1 are two required steps for apoptosome formation.Keywords
This publication has 33 references indexed in Scilit:
- Structure of the apoptotic protease-activating factor 1 bound to ADPNature, 2005
- Distinctive Roles of PHAP Proteins and Prothymosin-α in a Death Regulatory PathwayScience, 2003
- Three-Dimensional Structure of the ApoptosomeMolecular Cell, 2002
- Cytochrome c Promotes Caspase-9 Activation by Inducing Nucleotide Binding to Apaf-1Published by Elsevier BV ,2000
- An APAF-1·Cytochrome c Multimeric Complex Is a Functional Apoptosome That Activates Procaspase-9Published by Elsevier BV ,1999
- Induction of Apoptotic Program in Cell-Free Extracts: Requirement for dATP and Cytochrome cCell, 1996
- The C. elegans cell death gene ced-3 encodes a protein similar to mammalian interleukin-1β-converting enzymeCell, 1993
- A novel heterodimeric cysteine protease is required for interleukin-1βprocessing in monocytesNature, 1992
- Chromatin cleavage in apoptosis: Association with condensed chromatin morphology and dependence on macromolecular synthesisThe Journal of Pathology, 1984
- Glucocorticoid-induced thymocyte apoptosis is associated with endogenous endonuclease activationNature, 1980