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学科主题基础医学
PCAF-primed EZH2 acetylation regulates its stability and promotes lung adenocarcinoma progression
Wan, Junhu1,2,3; Zhan, Jun1,2,3; Li, Shuai1,2,3; Ma, Ji1,2,3; Xu, Weizhi1,2,3; Liu, Chang1,2,3; Xue, Xiaowei1,2,3; Xie, Yuping4; Fang, Weigang1,2,5; Chin, Y. Eugene6; Zhang, Hongquan1,2,3
刊名NUCLEIC ACIDS RESEARCH
2015-04-20
DOI10.1093/nar/gkv238
43期:7页:3591-3604
收录类别SCI
文章类型Article
WOS标题词Science & Technology
类目[WOS]Biochemistry & Molecular Biology
资助者Ministry of Science and Technology of China ; National Natural Science Foundation of China ; 111 Project of the Ministry of Education ; Beijing Natural Science Foundation ; Peking University ; Leading Academic Discipline Project of Beijing Education Bureau ; Ministry of Science and Technology of China ; National Natural Science Foundation of China ; 111 Project of the Ministry of Education ; Beijing Natural Science Foundation ; Peking University ; Leading Academic Discipline Project of Beijing Education Bureau
研究领域[WOS]Biochemistry & Molecular Biology
关键词[WOS]HISTONE METHYLTRANSFERASE ACTIVITY ; H3 LYSINE-27 METHYLATION ; PROSTATE-CANCER ; STEM-CELLS ; SUPPRESSES METHYLATION ; POLYCOMB ; PHOSPHORYLATION ; PROTEIN ; DIFFERENTIATION ; GENE
英文摘要

Enhancer of zeste homolog 2 (EZH2) is a key epigenetic regulator that catalyzes the trimethylation of H3K27 and is modulated by post-translational modifications (PTMs). However, the precise regulation of EZH2 PTMs remains elusive. We, herein, report that EZH2 is acetylated by acetyltransferase P300/CBP-associated factor (PCAF) and is deacetylated by deacetylase SIRT1. We identified that PCAF interacts with and acetylates EZH2 mainly at lysine 348 (K348). Mechanistically, K348 acetylation decreases EZH2 phosphorylation at T345 and T487 and increases EZH2 stability without disrupting the formation of polycomb repressive complex 2 (PRC2). Functionally, EZH2 K348 acetylation enhances its capacity in suppression of the target genes and promotes lung cancer cell migration and invasion. Further, elevated EZH2 K348 acetylation in lung adenocarcinoma patients predicts a poor prognosis. Our findings define a new mechanism underlying EZH2 modulation by linking EZH2 acetylation to its phosphorylation that stabilizes EZH2 and promotes lung adenocarcinoma progression.

语种英语
所属项目编号2015CB553906 ; 2013CB910501 ; 2013ZX09401004-006 ; 81230051 ; 30830048 ; 31170711 ; 81321003 ; 7120002 ; BMU20120314 ; BMU20130364
资助者Ministry of Science and Technology of China ; National Natural Science Foundation of China ; 111 Project of the Ministry of Education ; Beijing Natural Science Foundation ; Peking University ; Leading Academic Discipline Project of Beijing Education Bureau ; Ministry of Science and Technology of China ; National Natural Science Foundation of China ; 111 Project of the Ministry of Education ; Beijing Natural Science Foundation ; Peking University ; Leading Academic Discipline Project of Beijing Education Bureau
WOS记录号WOS:000354722500022
引用统计
被引频次:26[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
版本出版稿
条目标识符http://ir.bjmu.edu.cn/handle/400002259/59429
专题基础医学院_病理学系
作者单位1.Tsinghua Univ, Sch Life Sci, Beijing 100084, Peoples R China
2.Peking Univ, Hlth Sci Ctr, Minist Educ, Key Lab Carcinogenesis & Translat Res, Beijing 100191, Peoples R China
3.Peking Univ, Hlth Sci Ctr, State Key Lab Nat & Biomimet Drugs, Beijing 100191, Peoples R China
4.Peking Univ, Hlth Sci Ctr, Lab Mol Cell Biol & Tumor Biol, Dept Anat Histol & Embrol, Beijing 100191, Peoples R China
5.Peking Univ, Dept Pathol, Hlth Sci Ctr, Beijing 100191, Peoples R China
6.Chinese Acad Sci, Shanghai Jiao Tong Univ, Sch Med, Inst Hlth Sci,Shanghai Inst Biol Sci, Shanghai 200025, Peoples R China
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Wan, Junhu,Zhan, Jun,Li, Shuai,et al. PCAF-primed EZH2 acetylation regulates its stability and promotes lung adenocarcinoma progression[J]. NUCLEIC ACIDS RESEARCH,2015,43(7):3591-3604.
APA Wan, Junhu.,Zhan, Jun.,Li, Shuai.,Ma, Ji.,Xu, Weizhi.,...&Zhang, Hongquan.(2015).PCAF-primed EZH2 acetylation regulates its stability and promotes lung adenocarcinoma progression.NUCLEIC ACIDS RESEARCH,43(7),3591-3604.
MLA Wan, Junhu,et al."PCAF-primed EZH2 acetylation regulates its stability and promotes lung adenocarcinoma progression".NUCLEIC ACIDS RESEARCH 43.7(2015):3591-3604.
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