PHAPI, CAS, and Hsp70 Promote Apoptosome Formation by Preventing Apaf-1 Aggregation and Enhancing Nucleotide Exchange on Apaf-1
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چکیده
منابع مشابه
Calcium blocks formation of apoptosome by preventing nucleotide exchange in Apaf-1.
Apaf-1 plays an essential role in apoptosis. In the presence of cytochrome c and dATP, Apaf-1 assembles into an oligomeric apoptosome, which is responsible for the activation of procaspase-9 and the maintenance of the enzymatic activity of the processed caspase-9. Regulation of apoptosome assembly by other cellular factors is poorly understood. Here we report that physiological concentrations o...
متن کاملFormation of apoptosome is initiated by cytochrome c-induced dATP hydrolysis and subsequent nucleotide exchange on Apaf-1.
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...
متن کاملTaurine inhibits apoptosis by preventing formation of the Apaf-1/caspase-9 apoptosome.
Cardiomyocyte apoptosis contributes to cell death during myocardial infarction. One of the factors that regulate the degree of apoptosis during ischemia is the amino acid taurine. To study the mechanism underlying the beneficial effect of taurine, we examined the interaction between taurine and mitochondria-mediated apoptosis using a simulated ischemia model with cultured rat neonatal cardiomyo...
متن کاملRegulation of the Apaf-1-caspase-9 apoptosome.
caspase-9 apoptosome Shawn B. Bratton1 and Guy S. Salvesen2 1Division of Pharmacology and Toxicology, College of Pharmacy, and Center for Molecular and Cellular Toxicology, and Institute for Cellular and Molecular Biology, The University of Texas at Austin, Austin, TX 78712-0125, USA 2Program in Apoptosis and Cell Death Research, Sanford-Burnham Medical Research Institute, 10901 North Torrey Pi...
متن کاملThe Apaf-1 apoptosome induces formation of caspase-9 homo- and heterodimers with distinct activities
According to dogma, initiator caspases are activated through proximity-induced homodimerization, but some studies infer that during apoptosis caspase-9 may instead form a holoenzyme with the Apaf-1 apoptosome. Using several biochemical approaches, including a novel site-specific crosslinking technique, we provide the first direct evidence that procaspase-9 homodimerizes within the apoptosome, m...
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ژورنال
عنوان ژورنال: Molecular Cell
سال: 2008
ISSN: 1097-2765
DOI: 10.1016/j.molcel.2008.12.018