The Crosstalk Between Arginine Methylation and Serine Phosphorylation in Histone H3

组蛋白 H3 中精氨酸甲基化和丝氨酸磷酸化之间的串扰

• 批准号: 9244814
• 负责人: Cecilia Irene Zurita Lopez
• 金额: $ 14.6万
• 依托单位: CALIFORNIA STATE UNIVERSITY LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-03-16 至 2019-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9244814
• 关键词: Acetylation; Affect; Amino Acids; Arginine; BCL2 gene; Binding; Biochemistry; Biological Assay; Cell Death; Chromatin; DNA; Data; Disease; Environment; Enzymes; Event; FOXO1A gene; Foundations; Funding Opportunities; Gene Expression; Goals; Histone H3; Histones; Hydrogen; In Vitro; Investigation; Knowledge; Literature; Lysine; Mainstreaming; Malignant Neoplasms; Mammalian Cell; Methylation; Modification; Molecular Conformation; N-terminal; Peptides; Phosphorylation; Phosphoserine; Physiological; Play; Post-Translational Protein Processing; Protein-Arginine N-Methyltransferase; Proteins; Regulation; Reporting; Research; Role; Serine; Signal Pathway; Sodium Chloride; Tail; Testing; Ubiquitination; Work; base; graduate student; heterochromatin-specific nonhistone chromosomal protein HP-1; in vivo; inorganic phosphate; methyl group; prevent; protein protein interaction; public health relevance; undergraduate student

 DESCRIPTION (provided by applicant): Protein arginine methyltransferases (PRMTs) play key roles in regulating a multitude of cellular events. The methylated arginine residue itself serves to alter protein-protein interactions or enzymatic activities that are essential to specific signaling pathways. In addition, arginine methylation plays an important role in the regulation of proteins by either preventing or promoting the posttranslational modification of other neighboring residues. In addition to being involved in crosstalk with acetylation and ubiquitination, arginine methylation can affect phosphorylation. Regardless of the type of methylation mark (ADMA, SDMA or ω-MMA), the mechanism by which methylated arginines influence neighboring phosphorylated residues is unknown. In the case of the histone H3 tail, the addition of a phosphate group to serine-10 forms a salt bridge with arginine-8. The objective of this application is to explore the crosstalk between arginine-8 methylation and serine-10 phosphorylation in histone H3 whereby one modification alters the other. To accomplish this work, we will use both in vitro and in vivo methylation and phosphorylation assays. This work will elucidate the role of arginine methylation on phosphorylation, which is essential for understanding cellular biochemistry and physiological function.

 描述（由申请人提供）：蛋白质精氨酸甲基转移酶（PRMT）在调节多种细胞事件中发挥关键作用。甲基化精氨酸残基本身可以改变蛋白质-蛋白质相互作用或酶活性，这对于特定的 信号通路。此外，精氨酸甲基化通过阻止或促进其他邻近残基的翻译后修饰在蛋白质调节中发挥重要作用。除了参与乙酰化和泛素化的串扰之外，精氨酸甲基化还可以影响磷酸化。无论甲基化标记的类型（ADMA、SDMA 或 ω-MMA）如何，甲基化精氨酸影响邻近磷酸化残基的机制尚不清楚。对于组蛋白 H3 尾部，在丝氨酸 10 上添加磷酸基团与精氨酸 8 形成盐桥。本应用的目的是探索组蛋白 H3 中精氨酸 8 甲基化和丝氨酸 10 磷酸化之间的串扰，其中一种修饰会改变另一种修饰。为了完成这项工作，我们将使用体外和体内甲基化和磷酸化测定。这项工作将阐明精氨酸甲基化对磷酸化的作用，这对于理解细胞生物化学和生理功能至关重要。