CONTROL OF EUCARYOTIC FUNCTION BY METHYLATION

这项工作的目的是了解 S-腺苷甲硫氨酸依赖家族的几个相关成员 甲基转移酶与衰老、代谢控制和信号转导。 我们将继续我们的工作来鉴定L-异天冬氨酸(D- 天冬氨酸)O-甲基转移酶，识别年龄受损的蛋白质和 催化蛋白质修复反应的初始步骤。癫痫发作是以一种 这种酶在转基因基因敲除小鼠中功能丧失的结果。 我们将调查导致癫痫发作的因素以帮助 了解人类癫痫的发病机制及其潜在作用 控制力。我们将把这种蛋白质修复酶的作用与 我们最近发现的酶(反式乌头酸酯 甲基转移酶)识别一种自发形成的抑制物 潜在解毒反应中的柠檬酸循环。我们还提议 鉴定一个不断扩大的蛋白质精氨酸家族的成员 甲基转移酶。这些酶与信号分子相互作用 作为干扰素受体的TIS21蛋白和含SH3结构域 蛋白质。我们现在将对这些基因产物进行表征，以更好地 了解这些酶在代谢控制中的作用，包括 我们最近发现的一种新型酶，它使三角洲甲基化，或 内部胍基氮原子，或精氨酸残基。最后，我们会 研究催化An羧甲基化的酶 蛋白质合成中的伸长因子，可能受一种 甲基化/去甲基化循环。这些酶似乎都是 一个具有革命性血缘关系的家庭的成员，可能有共同的 三维结构。虽然有一组酶似乎可以 在减少潜在有毒产品积累方面的作用 在老化过程中自发产生，另一组 似乎可以调节细胞的新陈代谢及其信号转导 小路。

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.