Characterization and function of PARP10 in the control of cell physiology

adp核糖从NAD+向底物蛋白的转移是一个高度保守的翻译后机制，涉及广泛的生物学过程，包括细菌发病、细胞内信号传导、细胞分裂、基因转录、DNA修复和细胞凋亡。单adp核糖转移酶（mARTs）和多adp核糖聚合酶（PARPs）依赖于活性中心高度保守的谷氨酸残基进行催化。PARP家族有17个成员，是细胞内adp核糖基化酶的主要类别。出乎意料的是，我们发现PARP10（与其名称相反）具有mART活性，缺乏催化谷氨酸。我们的证据表明PARP10，可能还有其他parp，使用底物辅助催化adp -核糖酸残基，解释了为什么PARP10不能生成聚合物。此外，我们还发现了可能与P体和应力颗粒共享成分的PARP10病灶。为了了解PARP10的功能，我们打算验证和表征最近发现的潜在底物。此外，我们计划研究PARP10的底物特异性，并产生修饰特异性抗体。我们期望PARP10的详细分析将为细胞内mARTs的分析提供模型特征，并有助于阐明单adp与多adp核糖基化的不同生物学功能。

The transfer of ADP-ribose from NAD+ to substrate proteins is a highly conserved posttranslational mechanism, implicated in a broad range of biological processes, including bacterial pathogenesis, intracellular signaling, cell division, gene transcription, DNA repair, and apoptosis. Mono-ADP-ribosyltransferases (mARTs) and poly-ADP-ribose polymerases (PARPs) depend on a highly conserved glutamate residue in the active center for catalysis. The PARP family with 17 members is the major class of intracellular ADP-ribosylating enzymes. Unexpectedly, we found that PARP10 (contrary to its name) has mART activity and lacks the catalytic glutamate. Our evidence suggests that PARP10, and presumably other PARPs, ADP-ribosylate acidic residues using substrate-assisted catalysis, explaining why PARP10 cannot generate polymers. In addition we have identified PARP10 foci that might share components with P bodies and stress granules. To understand the function of PARP10 we intend to validate and characterize recently identified potential substrates. Furthermore we plan to investigate the substrate specificity of PARP10 and to generate modification-specific antibodies. We expect that the detailed analysis of PARP10 will have model character for the analysis of intracellular mARTs and help to illuminate the different biological functions of mono- versus poly-ADP-ribosylation.