PKB-mediated PHF20 phosphorylation on Ser291 is required for p53 function in DNA damage

被引：26

作者：

Li, Yuwen ^{[2
]}

Park, Jisoo ^{[2
]}

Piao, Longzhen ^{[2
,3
]}

Kong, Gyeyeong ^{[2
]}

Kim, Yongbaek ^{[2
]}

Park, Kyeong Ah ^{[2
]}

Zhang, Tiejun ^{[2
]}

Hong, Janghee ^{[2
]}

Hur, Gang Min ^{[2
]}

Seok, Jeong Ho ^{[2
]}

Choi, Seung-Won ^{[1
]}

Yoo, Byong Chul ^{[4
]}

Hemmings, Brian A. ^{[5
]}

Brazil, Derek P. ^{[6
]}

Kim, Seon-Hwan ^{[1
]}

Park, Jongsun ^{[2
]}

机构：

[1] Chungnam Natl Univ, Coll Med, Dept Neurosurg, Taejon 301131, South Korea

[2] Chungnam Natl Univ, Coll Med, Res Inst Med Sci, Dept Pharmacol,Canc Res Inst,Metab Dis & Cell Sig, Taejon 301131, South Korea

[3] Yanbian Univ, Affiliated Hosp, Dept Oncol, Jilin, Peoples R China

[4] Natl Canc Ctr, Res Inst & Hosp, Goyang 410769, South Korea

[5] Friedrich Miescher Inst Biomed Res, CH-4058 Basel, Switzerland

[6] Queens Univ Belfast, Sch Med Dent & Biomed Sci, Ctr Vis & Vasc Sci, Belfast BT12 6BA, Antrim, North Ireland

来源：

CELLULAR SIGNALLING | 2013年 / 25卷 / 01期

基金：

英国生物技术与生命科学研究理事会; 新加坡国家研究基金会;

关键词：

PHF20; Glioblastoma; PKB; p53; Protein phosphorylation; GLIOMA-EXPRESSED ANTIGEN-2; PROTEIN; KINASE; AKT; GLIOBLASTOMA; CANCER; MDM2; ACTIVATION; RESPONSES; PKB/AKT;

D O I：

10.1016/j.cellsig.2012.09.009

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

PHD finger protein 20 (PHF20) is a transcription factor, which was originally identified in glioma patients. PHF20 appears to be a novel antigen in glioma, and has also termed glioma-expressed antigen 2. PHF20 is thought to contribute to the development of cancers, including glioblastoma, lung cancer, colon cancer and ovarian cancer. However, little is known about the function of PHF20 in various cancers. Here we report that PHF20 contains two consensus sites for protein kinase B (PKB) phosphorylation (RxRxxS/T). PKB can directly phosphorylate PHF20 on Ser291 in vitro and in vivo. It has been shown that PKB participates in the tumor suppressor p53 regulated gene expression program and has a direct effect on p21 regulation after DNA damage. UV-induced DNA damage results in accumulation of p53 and PKB activation. Interestingly, PKB-mediated PHF20 phosphorylation led to an inhibition of p53 induction following UV treatment, leading to the reduction of p21 transcriptional activity. Using anti PHF20 and anti pPKB (S473) antibodies, these events were mapped in various human cancer tissues. Taken together, these data suggest that PHF20 is a novel substrate for PKB and its phosphorylation by PKB plays an important role in tumorigenesis via regulating of p53 mediated signaling. (C) 2012 Elsevier Inc. All rights reserved.

引用

页码：74 / 84

页数：11

共 43 条

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