Intracellular Mono-ADP-Ribosylation in Signaling and Disease.
Intracellular Mono-ADP-Ribosylation in Signaling and Disease.
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DOI：
10.3390/cells4040569
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发表时间：
2015-09-25
期刊：
影响因子：
6
通讯作者：
Lüscher B
中科院分区：
文献类型：
--
作者：
Bütepage M;Eckei L;Verheugd P;Lüscher B
调节蛋白质活性和细胞信号传导途径的关键过程是通过翻译后机制修饰蛋白质。关于附着和去除翻译后修饰的酶（写入器和擦除器）、被修饰的靶点以及由特定修饰引起的功能后果的知识，对于理解细胞生物学过程至关重要。此外，对这些机制和途径的详细了解有助于阐明各种疾病的分子原因，并确定治疗方法的潜在靶点。细胞内腺苷二磷酸（ADP）-核糖基化是指用ADP-核糖对蛋白质的烟酰胺腺嘌呤二核苷酸（NAD+）依赖性修饰，并且由ARTD（ADP-核糖基转移酶白喉毒素样，也称为PARP）家族的酶以及Sirtuin家族的一些成员催化。聚ADP-核糖基化是相对较好理解的，抑制剂被用作抗癌剂。然而，大多数ARTD酶和ADP-核糖基化Sirtuins限于催化单ADP-核糖基化。虽然胞内单ADP核糖基化的书写者、阅读者和擦除者只是最近才被确定，但越来越明显的是，这种可逆的翻译后修饰能够调节关键的胞内过程和信号通路。这些包括信号转导机制，与内质网和应激颗粒相关的应激途径，以及染色质相关的过程，如转录和DNA修复。我们假设单ADP核糖基化通过这些不同的途径控制癌症和传染病的发展。
A key process in the regulation of protein activities and thus cellular signaling pathways is the modification of proteins by post-translational mechanisms. Knowledge about the enzymes (writers and erasers) that attach and remove post-translational modifications, the targets that are modified and the functional consequences elicited by specific modifications, is crucial for understanding cell biological processes. Moreover detailed knowledge about these mechanisms and pathways helps to elucidate the molecular causes of various diseases and in defining potential targets for therapeutic approaches. Intracellular adenosine diphosphate (ADP)-ribosylation refers to the nicotinamide adenine dinucleotide (NAD+)-dependent modification of proteins with ADP-ribose and is catalyzed by enzymes of the ARTD (ADP-ribosyltransferase diphtheria toxin like, also known as PARP) family as well as some members of the Sirtuin family. Poly-ADP-ribosylation is relatively well understood with inhibitors being used as anti-cancer agents. However, the majority of ARTD enzymes and the ADP-ribosylating Sirtuins are restricted to catalyzing mono-ADP-ribosylation. Although writers, readers and erasers of intracellular mono-ADP-ribosylation have been identified only recently, it is becoming more and more evident that this reversible post-translational modification is capable of modulating key intracellular processes and signaling pathways. These include signal transduction mechanisms, stress pathways associated with the endoplasmic reticulum and stress granules, and chromatin-associated processes such as transcription and DNA repair. We hypothesize that mono-ADP-ribosylation controls, through these different pathways, the development of cancer and infectious diseases.