Regulation of p53 activity through lysine methylation

被引：657

作者：

Chuikov, S

Kurash, JK

Wilson, JR

Xiao, B

Justin, N

Ivanov, GS

McKinney, K

Tempst, P

Prives, C

Gamblin, SJ

Barlev, NA ^{[1
]}

Reinberg, D

机构：

[1] Robert Wood Johnson Med Sch, Dept Biochem, Howard Hughes Med Inst, Div Nucl Acids Enzymol, Piscataway, NJ 08854 USA

[2] NEMC Tufts Sch Med, Mol Oncol Res Inst, Boston, MA 02111 USA

[3] Natl Inst Med Res, MRC, Struct Biol Grp, London NW7 1AA, England

[4] Columbia Univ, Dept Biol Sci, New York, NY 10027 USA

[5] Mem Sloan Kettering Canc Ctr, Program Mol Biol, New York, NY 10021 USA

来源：

NATURE | 2004年 / 432卷 / 7015期

基金：

英国医学研究理事会; 美国国家卫生研究院;

关键词：

D O I：

10.1038/nature03117

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

引用

页码：353 / 360

页数：8

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