CONTROL OF EUCARYOTIC FUNCTION BY METHYLATION

通过甲基化控制真核功能

基本信息

批准号：
7154040
负责人：
STEVEN G CLARKE
金额：
$ 55.78万
依托单位：
UNIVERSITY OF CALIFORNIA LOS ANGELES
依托单位国家：
美国
项目类别：
财政年份：
1978
资助国家：
美国
起止时间：
1978-12-01 至 2009-11-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7154040
关键词：
Aconitic Acid Age Aging Aging-Related Process Amino Acyl Transfer RNA Arginine Brain Caenorhabditis elegans Carbon Cell division Cell physiology Cells Citric Acid Cycle Complex D Aspartate DNA Sequence Disease Drug Metabolic Detoxication Elongation Factor Enzyme Gene Enzymes Epilepsy Escherichia coli Family Genes Genome Goals Grant Health Human Hydrogen Interferon Receptor Investigation Knockout Mice Laboratories Lead Malignant Neoplasms Mammalian Cell Metabolic Control Metabolism Methods Methylation Methyltransferase Modification Nitrogen Numbers Open Reading Frames Organism Pathway interactions Peptides Phenotype Physiological Process Protein Biosynthesis Protein D-Aspartate-L-Isoaspartate Methyltransferase Protein phosphatase Protein-Arginine N-Methyltransferase Proteins RNA Binding Reaction Research Personnel Ribosomes Role SH3 Domains Saccharomyces cerevisiae Seizures Side Signal Transduction Signal Transduction Pathway Signaling Molecule Signaling Protein System Testing Transgenic Organisms Translations Work Yeasts aconitate methyltransferase beta-Aspartate cell growth regulation chemical group demethylation inhibitor/antagonist interest knockout animal loss of function member mouse model novel programs protein function protein-S-isoprenylcysteine O-methyltransferase repair enzyme repaired small molecule three dimensional structure trans-aconitate methyltransferase

项目摘要

The objective of this work is to understand the physiological role of several related members of a family of S-adenosylmethionine-dependent methyltransferases in aging, metabolic control, and signal transduction. We will continue our work to characterize the protein L-isoaspartate (D-aspartate) O-methyltransferase that recognizes age-damaged proteins and catalyzes the initial step of a protein repair reaction. Seizures occur as a result of the loss of function of this enzyme in transgenic knockout mice. We will investigate the factors leading to the onset of seizures to help understand the mechanisms involved in human epilepsy and its potential control. We will compare the role of this protein repair enzyme to an enzyme that we have recently discovered (trans-aconitate methyltransferase) that recognizes a spontaneously formed inhibitor of the citric acid cycle in a potential detoxification reaction. We also propose to characterize members of an expanding family of protein arginine methyltransferases. These enzymes interact with signaling molecules such as the interferon receptor, the TIS21 protein and SH3-domain-containing proteins. We will now characterize these gene products to better understand the role of these enzymes in metabolic control, including a novel enzyme we have recently discovered that methylates the delta, or internal guanidino nitrogen atom, of arginine residues. Finally, we will examine the enzymes that catalyze the carboxyl methylation of an elongation factor in protein synthesis that may be regulated by a methylation/demethylation cycle. These enzymes all appear to be members of one evolutionarily related family with a probable common three dimensional structure. While one group of enzymes appears to function in reducing the accumulation of the potentially toxic products generated spontaneously during the aging process, the other group appears to regulate the cell's metabolism and its signal transduction pathways.

这项工作的目的是了解几个的生理作用 S-腺苷甲硫代依赖性甲基转移酶家族的相关成员在衰老，代谢控制和信号转导。我们将继续我们的工作为了表征蛋白质L-异天冬氨酸（D-天冬氨酸）O-甲基转移酶识别年龄损坏的蛋白质并催化蛋白质修复的第一步反应。癫痫发作是由于该酶在转基因淘汰小鼠。我们将研究导致发作的因素癫痫发作以帮助了解人类癫痫及其涉及的机制潜在控制。我们将将这种蛋白质修复酶的作用与我们最近发现的酶（跨核酸甲基转移酶）识别在A中自发形成的柠檬酸周期抑制剂潜在的排毒反应。我们还建议表征扩大蛋白精氨酸甲基转移酶的家族。这些酶相互作用带有信号分子，例如干扰素受体，Tis21蛋白和含SH3域的蛋白质。我们现在将这些基因产品的特征更好地了解这些酶在代谢控制中的作用，包括新型酶，我们最近发现甲基化的三角洲或内部精氨酸残基的鸟养杆菌氮原子。最后，我们将研究催化蛋白质伸长因子的羧基甲基化的酶可以通过甲基化/去甲基化周期调节的合成。这些酶似乎都是一个与一个进化相关的家庭的成员可能的常见三维结构。而一组酶出现在减少潜在有毒产品的积累中起作用在衰老过程中自发生成，另一组似乎调节细胞的代谢及其信号转导途径。