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聚(ADP-核糖)糖水解酶是脆性X智力低下蛋白相关信使核糖核蛋白颗粒的一个组成部分。

Poly(ADP-ribose) glycohydrolase is a component of the FMRP-associated messenger ribonucleoparticles.

作者信息

Gagné Jean-Philippe, Bonicalzi Marie-Eve, Gagné Pierre, Ouellet Marie-Eve, Hendzel Michael J, Poirier Guy G

机构信息

Health and Environment Unit, Laval University Medical Research Center, CHUQ, Faculty of Medicine, Laval University, 2705 Boulevard Laurier, Ste-Foy, Québec, Canada, G1V 4G2.

出版信息

Biochem J. 2005 Dec 15;392(Pt 3):499-509. doi: 10.1042/BJ20050792.

Abstract

PARG [poly(ADP-ribose) glycohydrolase] is the only known enzyme that catalyses the hydrolysis of poly(ADP-ribose), a branched polymer that is synthesized by the poly(ADP-ribose) polymerase family of enzymes. Poly(ADP-ribosyl)ation is a transient post-translational modification that alters the functions of the acceptor proteins. It has mostly been studied in the context of DNA-damage signalling or DNA transaction events, such as replication and transcription reactions. Growing evidence now suggests that poly(ADP-ribosyl)ation could have a much broader impact on cellular functions. To elucidate the roles that could be played by PARG, we performed a proteomic identification of PARG-interacting proteins by mass spectrometric analysis of PARG pulled-down proteins. In the present paper, we report that PARG is resident in FMRP (Fragile-X mental retardation protein)-associated messenger ribonucleoparticles complexes. The localization of PARG in these complexes, which are components of the translation machinery, was confirmed by sedimentation and microscopy analysis. A functional link between poly(ADP-ribosyl)ation modulation and FMRP-associated ribonucleoparticle complexes are discussed in a context of translational regulation.

摘要

聚(ADP-核糖)糖苷水解酶(PARG)是唯一已知的催化聚(ADP-核糖)水解的酶,聚(ADP-核糖)是一种由聚(ADP-核糖)聚合酶家族的酶合成的分支聚合物。聚(ADP-核糖基)化是一种瞬时的翻译后修饰,可改变受体蛋白的功能。它主要是在DNA损伤信号传导或DNA交易事件(如复制和转录反应)的背景下进行研究的。现在越来越多的证据表明,聚(ADP-核糖基)化可能对细胞功能产生更广泛的影响。为了阐明PARG可能发挥的作用,我们通过对PARG下拉蛋白进行质谱分析,对PARG相互作用蛋白进行了蛋白质组学鉴定。在本文中,我们报告PARG存在于脆性X智力低下蛋白(FMRP)相关的信使核糖核蛋白颗粒复合物中。通过沉降和显微镜分析证实了PARG在这些作为翻译机制组成部分的复合物中的定位。在翻译调控的背景下讨论了聚(ADP-核糖基)化调节与FMRP相关核糖核蛋白复合物之间的功能联系。

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