聚（ADP - 核糖）与死亡相约。

Poly(ADP-ribose) makes a date with death.

作者信息

Heeres James T, Hergenrother Paul J

机构信息

Department of Chemistry, Roger Adams Laboratory, University of Illinois, Urbana, IL 61801, USA.

出版信息

Curr Opin Chem Biol. 2007 Dec;11(6):644-53. doi: 10.1016/j.cbpa.2007.08.038. Epub 2007 Oct 23.

DOI:10.1016/j.cbpa.2007.08.038

PMID:17936669

Abstract

Poly(ADP-ribose) polymerase (PARP) enzymes catalyze the conversion of NAD(+) to polymers of poly(ADP-ribose) (PAR). Although its role in the DNA-damage response has long been recognized, recent work indicates that PAR itself acts at the mitochondria to directly induce cell death through stimulation of apoptosis-inducing factor (AIF) release. This review discusses PAR synthesis and degradation, and the role of PAR misregulation in various disease states. Attention is given to opportunities for therapeutic intervention with small molecules that are involved in PAR signaling, with specific focus on poly(ADP-ribose) glycohydrolase (PARG) and AIF.

摘要

聚（ADP - 核糖）聚合酶（PARP）催化NAD（+）转化为聚（ADP - 核糖）（PAR）聚合物。尽管其在DNA损伤反应中的作用早已为人所知，但最近的研究表明，PAR本身在线粒体中发挥作用，通过刺激凋亡诱导因子（AIF）释放直接诱导细胞死亡。本文综述了PAR的合成与降解，以及PAR失调在各种疾病状态中的作用。重点关注了参与PAR信号传导的小分子治疗干预机会，特别关注聚（ADP - 核糖）糖苷水解酶（PARG）和AIF。