Apoptosis-inducing factor mediates poly(ADP-ribose) (PAR) polymer-induced cell death

被引：597

作者：

Yu, Seong-Woon

Andrabi, Shaida A.

Wang, Hongmin

Kim, No Soo

Poirier, Guy G.

Dawson, Ted M. ^{[1
]}

Dawson, Valina L.

机构：

[1] Johns Hopkins Univ, Sch Med, Inst Cell Engn, Dept Neurol, Baltimore, MD 21205 USA

[2] Johns Hopkins Univ, Sch Med, Inst Cell Engn, Dept Neurosci, Baltimore, MD 21205 USA

[3] Johns Hopkins Univ, Sch Med, Inst Cell Engn, Dept Physiol, Baltimore, MD 21205 USA

[4] CHU Quebec, Laval Univ Med Res Ctr, Hlth & Environm Unit, Ste Foy, PQ G1V 4G2, Canada

来源：

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA | 2006年 / 103卷 / 48期

关键词：

excitotoxicity; poly(ADP-ribose); polymerase;

D O I：

10.1073/pnas.0606528103

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Apoptosis-inducing factor (AIF), a mitochondrial oxidoreductase, is released into the cytoplasm to induce cell death in response to poly(ADP-ribose) (PAR) polymerase-1 (PARP-1) activation. How PARP-1 activation leads to AIF release is not known. Here we identify PAR polymer as a cell death signal that induces release of AIF. PAR polymer induces mitochondrial AIF release and translocation to the nucleus. PAR glycohydrolase, which degrades PAR polymer, prevents PAR P-1-dependent AIF release. Cells with reduced levels of AIF are resistant to PARP-1-dependent cell death and PAR polymer cytotoxicity. These results reveal PAR polymer as an AIF-releasing factor that plays important roles in PARP-1-dependent cell death.

引用

收藏

页码：18314 / 18319

页数：6

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