Regulation of p53 activity through lysine methylation
Regulation of p53 activity through lysine methylation
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DOI：
10.1038/nature03117
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发表时间：
2004-11-18
期刊：
影响因子：
64.8
通讯作者：
Reinberg, D
中科院分区：
文献类型：
--
作者：
Chuikov, S;Kurash, JK;Reinberg, D
P53是一种肿瘤抑制因子，调节细胞对基因毒性应激的反应。P53是一种短寿命蛋白，其活性主要通过不同的翻译后修饰来稳定调节。在这里，我们报道了一种通过Set9甲基转移酶的赖氨酸甲基化调控p53的新机制。Set9在羧基末端调控区的一个残基上特异性地甲基化p53。甲基化的p53局限于细胞核，这种修饰对其稳定性有积极影响。Set9以依赖于p53甲基化位点的方式调节p53靶基因的表达。Set9与p53肽及其辅因子产物s -腺苷- l-同型半胱氨酸（AdoHcy）的三元配合物的晶体结构为该赖氨酸甲基转移酶识别p53提供了分子基础。
p53 is a tumour suppressor that regulates the cellular response to genotoxic stresses. p53 is a short-lived protein and its activity is regulated mostly by stabilization via different post-translational modifications. Here we report a novel mechanism of p53 regulation through lysine methylation by Set9 methyltransferase. Set9 specifically methylates p53 at one residue within the carboxyl-terminus regulatory region. Methylated p53 is restricted to the nucleus and the modification positively affects its stability. Set9 regulates the expression of p53 target genes in a manner dependent on the p53-methylation site. The crystal structure of a ternary complex of Set9 with a p53 peptide and the cofactor product S-adenosyl-L-homocysteine (AdoHcy) provides the molecular basis for recognition of p53 by this lysine methyltransferase.