ASC is a Bax adaptor and regulates the p53-Bax mitochondrial apoptosis pathway

Takao Ohtsuka, Hoon Ryu, Yohji A. Minamishima, Salvador Macip, Junji Sagara, Keiichi I. Nakayama, Stuart A. Aaronson, Sam W. Lee

研究成果: Contribution to journalArticle査読

179 被引用数 (Scopus)

抄録

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 domain1-5. 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.

本文言語英語
ページ(範囲)121-128
ページ数8
ジャーナルNature Cell Biology
6
2
DOI
出版ステータス出版済み - 2 2004

All Science Journal Classification (ASJC) codes

  • Cell Biology

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