Cleaving the oxidative repair protein Ape1 enhances cell death mediated by granzyme A

被引：214

作者：

Fan, ZS

Beresford, PJ

Zhang, D

Xu, Z

Novina, CD

Yoshida, A

Pommier, Y

Lieberman, J ^{[1
]}

机构：

[1] Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA

[2] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA

[3] MIT, Ctr Canc Res, Cambridge, MA 02139 USA

[4] NCI, Mol Pharmacol Lab, Bethesda, MD 20892 USA

来源：

NATURE IMMUNOLOGY | 2003年 / 4卷 / 02期

关键词：

D O I：

10.1038/ni885

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

The cytolytic T lymphocyte protease granzyme A (GzmA) initiates a caspase-independent cell death pathway. Here we report that the rate-limiting enzyme of DNA base excision repair, apurinic endonuclease-1 (Ape1), which is also known as redox factor-1 (Ref-1), binds to GzmA and is contained in the SET complex, a macromolecular complex of 270-420 kDa that is associated with the endoplasmic reticulum and is targeted by GzmA during cell-mediated death. GzmA cleaves Ape1 after Lys31 and destroys its known oxidative repair functions. In so doing, GzmA may block cellular repair and force apoptosis. In support of this, cells with silenced Ape1 expression are more sensitive, whereas cells overexpressing noncleavable Ape1 are more resistant, to GzmA-mediated death.

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页码：145 / 153

页数：9

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