A novel site of AKT-mediated phosphorylation in the human MDM2 onco-protein

被引：38

作者：

Milne, D

Kampanis, P

Nicol, S

Dias, S

Campbell, DG

Fuller-Pace, F

Meek, D ^{[1
]}

机构：

[1] Univ Dundee, Mol Signaling Grp, Ctr Biomed Res, Dundee DD1 9SY, Scotland

[2] Univ Dundee, Ninewells Hosp & Med Sch, Dept Mol & Cellular Pathol, Dundee DD1 9SY, Scotland

[3] Univ Dundee, Sch Life Sci, MRC, Prot Phosphorylat Unit, Dundee DD1 4HN, Scotland

来源：

FEBS LETTERS | 2004年 / 577卷 / 1-2期

关键词：

MDM2; AKT; phosphorylation; p53; survival signaling;

D O I：

10.1016/j.febslet.2004.09.081

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

MDM2 is an E3 ubiquitin ligase which mediates ubiquitylation and proteasome-dependent degradation of the p53 tumor suppressor protein. Phosphorylation of MDM2 by the protein kinase AKT is thought to regulate MDM2 function in response to survival signals, but there has been uncertainty concerning the identity of the sites phosphorylated by AKT. In the present study, we identify Ser-166, a site previously reported as an AKT target, and Ser-188, a novel site which is the major site of phosphorylation of MDM2 by AKT in vitro. Analysis of MDM2 in cultured cells confirms that Ser-166 and Ser-188 are phosphorylated by AKT in a physiological context. (C) 2004 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

引用

收藏

页码：270 / 276

页数：7

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