Polo-like kinase-1 phosphorylates MDM2 at Ser260 and stimulates MDM2-mediated p53 turnover

被引：38

作者：

Dias, Sylvia S. ^{[1
]}

Hogan, Carol ^{[1
]}

Ochocka, Anna-Maria ^{[1
]}

Meek, David W. ^{[1
]}

机构：

[1] Univ Dundee, Ninewells Hosp & Med Sch, Biomed Res Inst, Dundee DD1 9SY, Scotland

来源：

FEBS LETTERS | 2009年 / 583卷 / 22期

关键词：

p53; Murne double-minute clone 2; Polo-like kinase-1; Phosphorylation; CULTURED-CELLS; PROTEIN; HDM2; BINDING; DOMAIN; PLK1; SITE; STABILITY; PATHWAY;

D O I：

10.1016/j.febslet.2009.09.057

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：

The E3 ubiqutin ligase, murne double-minute clone 2 (MDM2), promotes the degradation of p53 under normal homeostatic conditions. Several serine residues within the acidic domain of MDM2 are phosphorylated to maintain its activity but become hypo-phosphorylated following DNA damage, leading to inactivation of MDM2 and induction of p53. However, the signalling pathways that mediate these phosphorylation events are not fully understood. Here we show that the oncogenic and cell cycle-regulatory protein kinase, polo-like kinase-1 (PLK1), phosphorylates MDM2 at one of these residues, Ser260, and stimulates MDM2-mediated turnover of p53. These data are consistent with the idea that deregulation of PLK1 during tumourigenesis may help suppress p53 function. Structured summary: MINT-7266353: MDM2 (uniprotkb:Q00987) physically interacts (MI:0915) with PLK1 (uniprotkb:P53350) by pull down (MI:0096) MINT-7266344, MINT-7266329: MDM2 (uniprotkb:Q00987) physically interacts (MI:0915) with PLK1 (uniprotkb:P53350) by anti bait coimmunoprecipitation (MI:0006) MINT-7266250: PLK1 (uniprotkb:P53350) phosphorylates (MI:0217) p53 (uniprotkb:P04637) by protein kinase assay (MI:0424) MINT-7266241, MINT-7266318: PLK1 (uniprotkb:P53350) phosphorylates (MI:0217) MDM2 (uniprotkb:P23804) by protein kinase assay (MI:0424) MINT-7266231, MINT-7266805, MINT-7266264, MINT-7266299: PLK1 (uniprotkb:P53350) phosphorylates (MI:0217) MDM2 (uniprotkb:Q00987) by protein kinase assay (MI:0424) (C) 2009 Published by Elsevier B. V. on behalf of the Federation of European Biochemical Societies.

引用

页码：3543 / 3548

页数：6

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