核酸内切酶G：一种在细胞凋亡时释放的线粒体蛋白，参与不依赖半胱天冬酶的DNA降解。

Endonuclease G: a mitochondrial protein released in apoptosis and involved in caspase-independent DNA degradation.

作者信息

van Loo G, Schotte P, van Gurp M, Demol H, Hoorelbeke B, Gevaert K, Rodriguez I, Ruiz-Carrillo A, Vandekerckhove J, Declercq W, Beyaert R, Vandenabeele P

机构信息

Flanders Interuniversity Institute for Biotechnology and Ghent University, Department of Molecular Biology, K.L. Ledeganckstraat 35, B-9000 Ghent, Belgium.

出版信息

Cell Death Differ. 2001 Dec;8(12):1136-42. doi: 10.1038/sj.cdd.4400944.

DOI:10.1038/sj.cdd.4400944

PMID:11753562

Abstract

A hallmark of apoptosis is the fragmentation of nuclear DNA. Although this activity involves the caspase-3-dependent DNAse CAD (caspase-activated DNAse), evidence exists that DNA fragmentation can occur independently of caspase activity. Here we report on the ability of truncated Bid (tBid) to induce the release of a DNAse activity from mitochondria. This DNAse activity was identified by mass spectrometry as endonuclease G, an abundant 30 kDa protein released from mitochondria under apoptotic conditions. No tBid-induced endonuclease G release could be observed in mitochondria from Bcl-2-transgenic mice. The in vivo occurrence of endonuclease G release from mitochondria during apoptosis was confirmed in the liver from mice injected with agonistic anti-Fas antibody and is completely prevented in Bcl-2 transgenic mice. These data indicate that endonuclease G may be involved in CAD-independent DNA fragmentation during cell death pathways in which truncated Bid is generated.

摘要

细胞凋亡的一个标志是核DNA片段化。尽管这一过程涉及依赖半胱天冬酶-3的DNA酶CAD（半胱天冬酶激活的DNA酶），但有证据表明DNA片段化可独立于半胱天冬酶活性而发生。在此，我们报告截短型Bid（tBid）诱导线粒体释放一种DNA酶活性的能力。通过质谱鉴定，这种DNA酶活性为核酸内切酶G，它是一种在凋亡条件下从线粒体释放的丰富的30 kDa蛋白。在Bcl-2转基因小鼠的线粒体中未观察到tBid诱导的核酸内切酶G释放。在注射了抗Fas激动性抗体的小鼠肝脏中，证实了凋亡期间线粒体中核酸内切酶G释放的体内发生情况，而在Bcl-2转基因小鼠中这种情况完全被阻止。这些数据表明，在产生截短型Bid的细胞死亡途径中，核酸内切酶G可能参与了不依赖CAD的DNA片段化过程。