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ASC is a Bax adaptor and regulates the p53–Bax mitochondrial apoptosis pathway
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ASC is a Bax adaptor and regulates the p53–Bax mitochondrial apoptosis pathway
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Journal Article
ASC is a Bax adaptor and regulates the p53–Bax mitochondrial apoptosis pathway
2004
Overview
The apoptosis-associated speck-like protein (ASC) is an unusual adaptor protein that contains the Pyrin/PAAD death domain in addition to the CARD protein–protein interaction domain
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. Here, we present evidence that ASC can function as an adaptor molecule for Bax and regulate a p53–Bax mitochondrial pathway of apoptosis. When ectopically expressed, ASC interacted directly with Bax, colocalized with Bax to the mitochondria, induced cytochrome
c
release with a significant reduction of mitochondrial membrane potential and resulted in the activation of caspase-9, -2 and -3. The rapid induction of apoptosis by ASC was not observed in Bax-deficient cells. We also show that induction of ASC after exposure to genotoxic stress is dependent on p53. Blocking of endogenous ASC expression by small-interfering RNA (siRNA) reduced the apoptotic response and inhibited translocation of Bax to mitochondria in response to p53 or genotoxic insult, suggesting that ASC is required to translocate Bax to the mitochondria. Our findings demonstrate that ASC has an essential role in the intrinsic mitochondrial pathway of apoptosis through a p53–Bax network.
Publisher
Nature Publishing Group UK,Nature Publishing Group
Subject
/ Biomedical and Life Sciences
/ CARD Signaling Adaptor Proteins
/ Cytoskeletal Proteins - genetics
/ Cytoskeletal Proteins - metabolism
/ Humans
/ letter
/ Membrane Potentials - physiology
/ Protein-protein interactions
/ Proto-Oncogene Proteins - genetics
/ Proto-Oncogene Proteins - metabolism
/ Proto-Oncogene Proteins c-bcl-2
/ Recombinant Fusion Proteins - genetics
/ Recombinant Fusion Proteins - metabolism
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