CONTROL OF EUCARYOTIC FUNCTION BY METHYLATION

这项工作的目的是了解的生理作用， S-腺苷甲硫氨酸依赖性 甲基转移酶在衰老、代谢控制和信号转导中的作用。 我们将继续我们的工作，以表征蛋白质L-异天冬氨酸（D- 天冬氨酸）O-甲基转移酶，其识别年龄损伤蛋白， 催化蛋白质修复反应的初始步骤。癫痫发作是由于 转基因敲除小鼠中这种酶功能丧失的结果。 我们将调查导致癫痫发作的因素，以帮助 了解人类癫痫的机制及其潜力 控制我们将比较这种蛋白质修复酶的作用， 我们最近发现的酶（trans-aconitate 甲基转移酶），其识别自发形成的 柠檬酸循环中潜在的解毒反应。我们亦建议 来描述一个不断扩大的精氨酸蛋白家族的成员， 甲基转移酶这些酶与信号分子相互作用， 作为干扰素受体，TIS 21蛋白和含SH 3结构域的 proteins.我们现在将描述这些基因产物，以更好地 了解这些酶在代谢控制中的作用，包括 我们最近发现了一种新的酶，它使δ甲基化， 内部胍基氮原子或精氨酸残基。最后我们将 研究催化羧基甲基化的酶， 蛋白质合成中的延伸因子，其可由 甲基化/去甲基化循环。这些酶似乎都是 一个革命家庭的成员，可能有一个共同的 三维结构虽然一组酶似乎 在减少潜在有毒产物的积累方面的作用 在衰老过程中自发产生的，另一组 似乎可以调节细胞的新陈代谢及其信号转导 途径。

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, or 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 revolutionarily related family with a probably 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.