Aven, a novel inhibitor of caspase activation, binds Bcl-xL and Apaf-1

被引：152

作者：

Chau, BN

Cheng, EHY

Kerr, DA

Hardwick, JM ^{[1
]}

机构：

[1] Johns Hopkins Univ, Sch Med, Dept Pharmacol & Mol Sci, Baltimore, MD 21205 USA

[2] Johns Hopkins Univ, Sch Med, Dept Neurol, Baltimore, MD 21205 USA

[3] Johns Hopkins Univ, Sch Med, Dept Mol Microbiol & Immunol, Baltimore, MD 21205 USA

[4] Johns Hopkins Univ, Sch Publ Hlth, Dept Pharmacol & Mol Sci, Baltimore, MD 21205 USA

[5] Johns Hopkins Univ, Sch Publ Hlth, Dept Neurol, Baltimore, MD 21205 USA

[6] Johns Hopkins Univ, Sch Publ Hlth, Dept Mol Microbiol & Immunol, Baltimore, MD 21205 USA

来源：

MOLECULAR CELL | 2000年 / 6卷 / 01期

关键词：

D O I：

10.1016/S1097-2765(00)00005-8

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Bcl-x(L), an antiapoptotic Bcl-2 family member, is postulated to function at multiple stages in the cell death pathway. The possibility that Bcl-x(L) inhibits cell death at a late (postmitochondrial) step in the death pathway is supported by this report of a novel apoptosis inhibitor, Aven, which binds to both Bcl-x(L) and the caspase regulator, Apaf-1. Identified in a yeast two-hybrid screen, Aven is broadly expressed and is conserved in other mammalian species. Only those mutants of Bcl-x(L) that retain their antiapoptotic activity are capable of binding Aven. Aven interferes with the ability of Apaf-1 to self-associate, suggesting that Aven impairs Apaf-1-mediated activation of caspases. Consistent with this idea, Aven inhibited the proteolytic activation of caspases in a cell-free extract and suppressed apoptosis induced by Apaf-1 plus caspase-9. Thus, Aven represents a new class of cell death regulator.

引用

页码：31 / 40

页数：10

共 55 条

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