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Sci. STKE, 10 February 2004
Vol. 2004, Issue 219, p. tw58
[DOI: 10.1126/stke.2192004TW58]

EDITORS' CHOICE

APOPTOSIS ASCing for BAX

Apoptosis-associated speck-like protein (ASC) is inactivated in about 40% of breast cancers. Its expression is induced in response to the tumor suppressor protein p53 and to DNA damage. Ohtsuka et al. have now identified a p53-binding sequence in promoter of the ASC gene. Overexpression of ASC in a human carcinoma cell line increased apoptosis. This required the expression of Bax, a proapoptotic protein whose expression is also driven by p53. Bax induces the release of cytochrome c from mitochondria and disrupts mitochondrial function. Like Bax, ASC also translocated and colocalized to the mitochondria in response to genotoxic stress. The two proteins also associated in a complex when overexpressed. Suppression of endogenous ASC expression by RNA interference decreased Bax translocation to the mitochondria, p53-mediated cell death, and cell death resulting from genotoxic agents. The absence of ASC also correlated to the lack of conformational change in Bax associated with its translocation. The authors propose that ASC functions as a downstream effector of p53 in DNA-damage-mediated cell death through the Bax pathway and that binding of ASC to Bax may protect Bax from inactivation and facilitate Bax's effect on the mitochondria.

T. Ohtsuka, H. Ryu, Y. A. Minamishima, S. Macip, J. Sagara, K. I. Nakayama, S. A. Aaronson, S. W. Lee, ASC is a Bax adaptor and regulates the p53-Bax mitochondria apoptosis pathway. Nat. Cell Biol. 6, 121-128 (2004). [Online Journal]

Citation: ASCing for BAX. Sci. STKE 2004, tw58 (2004).


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