Players in ADP-ribosylation: Readers and Erasers.
Players in ADP-ribosylation: Readers and Erasers.
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ADP-核糖基化中的参与者：读取器和擦除器。
DOI：
10.2174/1389203717666160419144846
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发表时间：
2016
影响因子：
2.8
通讯作者：
B. Lüscher
中科院分区：
文献类型：
--
作者：
Patricia Verheugd;Mareike Bütepage;Laura Eckei;B. Lüscher
ADP-核糖化描述了一种古老且高度保守的蛋白质翻译后修饰(PTM)。已发现许多细胞过程受ADP-核糖化调控，包括DNA修复、基因转录和信号传递过程。催化ADP核糖化的酶利用NAD+作为辅因子，在烟酰胺释放的情况下将ADP核糖转移到底物上。在哺乳动物中，已经描述了细胞外和细胞内的酶。ADP核糖基化是由ADP核糖基转移酶(ARTS)和一些sirtuins催化的。细胞外ARTS和细胞内ART分别属于霍乱毒素样(ARTC)和白喉毒素样(ARTD)亚类。ARTD可以根据它们产生多ADP核糖链的能力或与单ADP核糖化底物的能力而进一步细分。与后者类似，ARTCs和sirtuins仅限于单-ADP-核糖化。最近的发现提供了有关ADP-核糖化的功能后果的信息。与其他PTM类似，ADP-核糖基化可以对酶施加变构效应，从而控制其催化活性。此外，这种PTM可以被多个蛋白质基序和结构域所读取，这些基序和结构域介导了蛋白质之间的相互作用。通常，这些读者可以区分单-ADP核糖化和多-ADP-核糖化。此外，由于描述了可以消除ADP-核糖化的蛋白质，这种翻译后修饰是完全可逆的，从而提供了一种额外的机制来瞬时控制蛋白质的功能和网络。在这篇综述中，我们将描述与ADP-核糖化过程相关的基序和结构域的最新发现，尤其是阅读器和擦除器。这些新的发现为ADP-核糖化的广泛功能作用和促成这种修饰的下游后果的高度多样性的机制提供了证据。
ADP-ribosylation describes an ancient and highly conserved posttranslational modification (PTM) of proteins. Many cellular processes have been identified that are regulated by ADP-ribosylation, including DNA repair, gene transcription and signaling processes. Enzymes catalyzing ADP-ribosylation use NAD+ as a cofactor to transfer ADP-ribose to a substrate under release of nicotinamide. In mammals extracellular and intracellular enzymes have been described. ADP-ribosylation is catalyzed by ADP-ribosyltransferases (ARTs) and some Sirtuins. Extracellular and intracellular ARTs belong to the cholera toxin-like (ARTC) and the diphtheria toxin-like (ARTD) subclass, respectively. ARTDs can be further subdivided depending on their ability to either generate poly-ADP-ribose chains, or to mono-ADP-ribosylate substrates. Similar to the latter, ARTCs and Sirtuins are restricted to mono-ADP-ribosylation. Recent findings have provided information about the functional consequences of ADP-ribosylation. Analogous to other PTMs, ADP-ribosylation can exert allosteric effects on enzymes, thereby controlling their catalytic activity. Moreover, this PTM can be read by multiple protein motifs and domains mediating protein-protein interactions. Typically these readers can distinguish between mono- and poly-ADP-ribosylation. Furthermore, with the description of proteins that can erase ADP-ribosylation, this posttranslational modification is fully reversible and thus provides an additional mechanism to transiently control protein functions and networks. In this review we will describe the most recent findings on motifs and domains that are related to ADP-ribosylation processes with a particular focus on readers and erasers. These new findings provide evidence for broad functional roles of ADP-ribosylation and a high diversity of mechanisms that contribute to the downstream consequences of this modification.