Please use this identifier to cite or link to this item:
Title: ASC is a Bax adaptor and regulates the p53-Bax mitochondrial apoptosis pathway.
Authors: Ohtsuka, T.
Ryu, H.
Minamishima, Y. A.
Macip, S.
Sagara, J.
Nakayama, K. I.
Aaronson, S. A.
Lee, S. W.
First Published: Feb-2004
Citation: NAT CELL BIOL, 2004, 6 (2), pp. 121-128
Abstract: 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. 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.
DOI Link: 10.1038/ncb1087
ISSN: 1465-7392
Type: Journal Article
Appears in Collections:Published Articles, Dept. of Biochemistry

Files in This Item:
There are no files associated with this item.

Items in LRA are protected by copyright, with all rights reserved, unless otherwise indicated.