Modulation of DNA Methyltransferases by S-Nitrosylation

通过 S-亚硝基化调节 DNA 甲基转移酶

• 批准号: 6999590
• 负责人: Byron H Lee
• 金额: $ 4.14万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-09-30 至 2008-09-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6999590
• 关键词: CpG islands; DNA methylation; affinity chromatography; biotin; carcinogenesis; cell line; cysteine; enzyme activity; inflammation; liquid chromatography mass spectrometry; methyltransferase; nitric oxide; nitroso compounds; oxidizing agents; pepsin; protein degradation; proteomics; recombinant proteins; site directed mutagenesis; trypsin

DESCRIPTION (provided by applicant): The focus of this research project is to study the effects of S-nitrosylation on the enzymatic activities of the mammalian DNA methyltransferases. Alterations in DNA methylation patterns are among the earliest and most common changes observed in cancer. Moreover, in many cancers such as liver, esophageal, gastric, colorectal, and bladder, chronic inflammation has been shown to play a causative role in carcinogenesis. Immune cells in inflammatory lesions produce significant amounts of microbicidal oxidants such as nitric oxide and superoxide that can have profound unintended effects on somatic cells, leading to carcinogenesis. The hypothesis to be explored in this project is that nitric oxide mediated S-nitrosylation of DNA methyltransferase enzymes modulates their activities in a manner that can alter DNA methylation patterns to promote carcinogenesis.

描述（由申请人提供）：本研究项目的重点是研究S-亚硝基化对哺乳动物DNA甲基转移酶酶活性的影响。DNA甲基化模式的改变是在癌症中观察到的最早和最常见的变化之一。此外，在许多癌症如肝癌、食道癌、胃癌、结肠直肠癌和膀胱癌中，慢性炎症已被证明在致癌作用中起致病作用。炎性病变中的免疫细胞产生大量的杀微生物氧化剂，如一氧化氮和超氧化物，这些氧化剂可能对体细胞产生深远的意外影响，导致致癌作用。在这个项目中要探讨的假设是，一氧化氮介导的S-亚硝基化的DNA甲基转移酶调节其活动的方式，可以改变DNA甲基化模式，以促进致癌作用。