Characterization and function of PARP10 in the control of cell physiology

PARP10 在细胞生理学控制中的特性和功能

• 批准号: 136828175
• 负责人: Professor Dr. Bernhard Lüscher
• 金额: --
• 依托单位: Institut für Biochemie und Molekularbiologie
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2009
• 资助国家: 德国
• 起止时间: 2008-12-31 至 2012-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/136828175?language=en
• 关键词: Characterization; function; PARP10; control; cell

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.

ADP-核糖从NAD+转移到底物蛋白是一种高度保守的翻译后机制，涉及广泛的生物学过程，包括细菌发病机制、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核糖基转移酶（mARTs）和聚ADP核糖聚合酶（PARP）依赖于活性中心中高度保守的谷氨酸残基进行催化。具有17个成员的PARP家族是细胞内ADP-核糖基化酶的主要类别。出乎意料的是，我们发现PARP 10（与其名称相反）具有mART活性，并且缺乏催化谷氨酸。我们的证据表明，PARP 10和其他可能的PARPs，ADP-核糖基酸酸性残基使用底物辅助催化，解释了为什么PARP 10不能产生聚合物。此外，我们已经确定了PARP 10灶，可能共享组件与P体和应力颗粒。为了了解PARP 10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PARP 10的底物特异性并产生修饰特异性抗体。我们预计PARP 10的详细分析将具有细胞内mART分析的模型特征，并有助于阐明单ADP核糖基化与多ADP核糖基化的不同生物学功能。