title: PCAF-primed EZH2 acetylation regulates its stability and promotes lung adenocarcinoma progression.
abstract: 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.
authors: Key Laboratory of Carcinogenesis and Translational Research, Ministry of Education, and State Key Laboratory of Natural and Biomimetic Drugs, Peking University Health Science Center, Beijing 100191, China Laboratory of Molecular Cell Biology and Tumor Biology, Department of Anatomy, Histology and Embrology, Peking University Health Science Center, Beijing 100191, China.
authors: Junhu
authors: J
authors: Wan
authors: Key Laboratory of Carcinogenesis and Translational Research, Ministry of Education, and State Key Laboratory of Natural and Biomimetic Drugs, Peking University Health Science Center, Beijing 100191, China Laboratory of Molecular Cell Biology and Tumor Biology, Department of Anatomy, Histology and Embrology, Peking University Health Science Center, Beijing 100191, China.
authors: Jun
authors: J
authors: Zhan
authors: Key Laboratory of Carcinogenesis and Translational Research, Ministry of Education, and State Key Laboratory of Natural and Biomimetic Drugs, Peking University Health Science Center, Beijing 100191, China Laboratory of Molecular Cell Biology and Tumor Biology, Department of Anatomy, Histology and Embrology, Peking University Health Science Center, Beijing 100191, China.
authors: Shuai
authors: S
authors: Li
authors: Key Laboratory of Carcinogenesis and Translational Research, Ministry of Education, and State Key Laboratory of Natural and Biomimetic Drugs, Peking University Health Science Center, Beijing 100191, China Laboratory of Molecular Cell Biology and Tumor Biology, Department of Anatomy, Histology and Embrology, Peking University Health Science Center, Beijing 100191, China.
authors: Ji
authors: J
authors: Ma
authors: Key Laboratory of Carcinogenesis and Translational Research, Ministry of Education, and State Key Laboratory of Natural and Biomimetic Drugs, Peking University Health Science Center, Beijing 100191, China Laboratory of Molecular Cell Biology and Tumor Biology, Department of Anatomy, Histology and Embrology, Peking University Health Science Center, Beijing 100191, China.
authors: Weizhi
authors: W
authors: Xu
authors: Key Laboratory of Carcinogenesis and Translational Research, Ministry of Education, and State Key Laboratory of Natural and Biomimetic Drugs, Peking University Health Science Center, Beijing 100191, China Laboratory of Molecular Cell Biology and Tumor Biology, Department of Anatomy, Histology and Embrology, Peking University Health Science Center, Beijing 100191, China.
authors: Chang
authors: C
authors: Liu
authors: Key Laboratory of Carcinogenesis and Translational Research, Ministry of Education, and State Key Laboratory of Natural and Biomimetic Drugs, Peking University Health Science Center, Beijing 100191, China Laboratory of Molecular Cell Biology and Tumor Biology, Department of Anatomy, Histology and Embrology, Peking University Health Science Center, Beijing 100191, China.
authors: Xiaowei
authors: X
authors: Xue
authors: School of Life Sciences, Tsinghua University, Beijing 100084, China.
authors: Yuping
authors: Y
authors: Xie
authors: Key Laboratory of Carcinogenesis and Translational Research, Ministry of Education, and State Key Laboratory of Natural and Biomimetic Drugs, Peking University Health Science Center, Beijing 100191, China Department of Pathology, Peking University Health Science Center, Beijing 100191, China.
authors: Weigang
authors: W
authors: Fang
authors: Institute of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai Jiaotong University School of Medicine, Shanghai 200025, China.
authors: Y Eugene
authors: YE
authors: Chin
authors: Key Laboratory of Carcinogenesis and Translational Research, Ministry of Education, and State Key Laboratory of Natural and Biomimetic Drugs, Peking University Health Science Center, Beijing 100191, China Laboratory of Molecular Cell Biology and Tumor Biology, Department of Anatomy, Histology and Embrology, Peking University Health Science Center, Beijing 100191, China Hongquan.Zhang@bjmu.edu.cn.
authors: Hongquan
authors: H
authors: Zhang
mesh_terms: D000107:Acetylation; D000230:Adenocarcinoma / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D018450:Disease Progression; D000071221:Enhancer of Zeste Homolog 2 Protein; D020868:Gene Silencing; D057809:HEK293 Cells; D006801:Humans; D008175:Lung Neoplasms / Q000378:metabolism* / Q000473:pathology; D013058:Mass Spectrometry; D009362:Neoplasm Metastasis; D063151:Polycomb Repressive Complex 2 / Q000235:genetics / Q000378:metabolism*; D055550:Protein Stability; D056564:Sirtuin 1 / Q000378:metabolism; D050880:p300-CBP Transcription Factors / Q000378:metabolism*; D000099224:p300-CBP-Associated Factor
chemical_list: D000071221:Enhancer of Zeste Homolog 2 Protein; D063151:Polycomb Repressive Complex 2; D056564:Sirtuin 1; D050880:p300-CBP Transcription Factors; D000099224:p300-CBP-Associated Factor; C498409:EZH2 protein, human; C447939:SIRT1 protein, human