Crosstalk between poly(ADP-ribose) polymerase and sirtuin enzymes.

Crosstalk between poly(ADP-ribose) polymerase and sirtuin enzymes.
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聚(ADP-核糖)聚合酶和沉默调节蛋白酶之间的串扰。

DOI:
10.1016/j.mam.2013.01.004
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发表时间:
2013-12
影响因子:
10.6
通讯作者:
Bai, Peter
Bai, Peter
中科院分区:
医学1区
文献类型:
--
作者:
Canto, Caries;Sauve, Anthony A.;Bai, Peter

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聚(adp -核糖)聚合酶(PARPs)是NAD+依赖性酶,被确定为DNA修复蛋白,然而,今天似乎很清楚PARPs负责过多的生物学功能。Sirtuins (SIRTs)是NAD+依赖的脱乙酰酶,与PARP参与相同的生物学过程,这引发了PARP和SIRT酶是否在生理和病理生理条件下相互作用的问题。在此,我们回顾了目前对SIRT-PARP相互作用的理解,包括相互作用的生化性质(对共同NAD+底物的竞争,相互的翻译后修饰和直接转录效应)以及相互作用的生理或病理生理后果(代谢事件,氧化应激反应,基因组稳定性和衰老)。最后,我们概述了通过药物干预直接或通过调节NAD+稳态来调节PARP和SIRT酶的可能性。
Poly(ADP-ribose) polymerases (PARPs) are NAD+ dependent enzymes that were identified as DNA repair proteins, however, today it seems clear that PARPs are responsible for a plethora of biological functions. Sirtuins (SIRTs) are NAD+-dependent deacetylase enzymes involved in the same biological processes as PARPs raising the question whether PARP and SIRT enzymes may interact with each other in physiological and pathophysiological conditions. Hereby we review the current understanding of the SIRT-PARP interplay in regard to the biochemical nature of the interaction (competition for the common NAD+ substrate, mutual posttranslational modifications and direct transcriptional effects) and the physiological, or pathophysiological consequences of the interactions (metabolic events, oxidative stress response, genomic stability and ageing). Finally, we give an overview of the possibilities of pharmacological intervention to modulate PARP and SIRT enzymes either directly, or through modulating NAD+ homeostasis.
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