Regulation of EZH2 by SMYD2-Mediated Lysine Methylation Is Implicated in Tumorigenesis
Yi Zeng,
Rongfang Qiu,
Yang Yang,
Tianyang Gao,
Yu Zheng,
Wei Huang,
Jie Gao,
Kai Zhang,
Ruiqiong Liu,
Shuang Wang,
Yongqiang Hou,
Wenqian Yu,
Shuai Leng,
Dandan Feng,
Wei Liu,
Xi Zhang,
Yan Wang
Affiliations
Yi Zeng
2011 Collaborative Innovation Center of Tianjin for Medical Epigenetics, Tianjin Key Laboratory of Cellular and Molecular Immunology, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin 300070, China
Rongfang Qiu
2011 Collaborative Innovation Center of Tianjin for Medical Epigenetics, Tianjin Key Laboratory of Cellular and Molecular Immunology, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin 300070, China
Yang Yang
2011 Collaborative Innovation Center of Tianjin for Medical Epigenetics, Tianjin Key Laboratory of Cellular and Molecular Immunology, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin 300070, China
Tianyang Gao
2011 Collaborative Innovation Center of Tianjin for Medical Epigenetics, Tianjin Key Laboratory of Cellular and Molecular Immunology, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin 300070, China
Yu Zheng
2011 Collaborative Innovation Center of Tianjin for Medical Epigenetics, Tianjin Key Laboratory of Cellular and Molecular Immunology, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin 300070, China
Wei Huang
2011 Collaborative Innovation Center of Tianjin for Medical Epigenetics, Tianjin Key Laboratory of Cellular and Molecular Immunology, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin 300070, China
Jie Gao
2011 Collaborative Innovation Center of Tianjin for Medical Epigenetics, Tianjin Key Laboratory of Cellular and Molecular Immunology, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin 300070, China
Kai Zhang
2011 Collaborative Innovation Center of Tianjin for Medical Epigenetics, Tianjin Key Laboratory of Cellular and Molecular Immunology, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin 300070, China
Ruiqiong Liu
2011 Collaborative Innovation Center of Tianjin for Medical Epigenetics, Tianjin Key Laboratory of Cellular and Molecular Immunology, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin 300070, China
Shuang Wang
2011 Collaborative Innovation Center of Tianjin for Medical Epigenetics, Tianjin Key Laboratory of Cellular and Molecular Immunology, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin 300070, China
Yongqiang Hou
2011 Collaborative Innovation Center of Tianjin for Medical Epigenetics, Tianjin Key Laboratory of Cellular and Molecular Immunology, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin 300070, China
Wenqian Yu
2011 Collaborative Innovation Center of Tianjin for Medical Epigenetics, Tianjin Key Laboratory of Cellular and Molecular Immunology, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin 300070, China
Shuai Leng
2011 Collaborative Innovation Center of Tianjin for Medical Epigenetics, Tianjin Key Laboratory of Cellular and Molecular Immunology, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin 300070, China
Dandan Feng
2011 Collaborative Innovation Center of Tianjin for Medical Epigenetics, Tianjin Key Laboratory of Cellular and Molecular Immunology, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin 300070, China
Wei Liu
2011 Collaborative Innovation Center of Tianjin for Medical Epigenetics, Tianjin Key Laboratory of Cellular and Molecular Immunology, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin 300070, China
Xi Zhang
School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang 325000, China
Yan Wang
2011 Collaborative Innovation Center of Tianjin for Medical Epigenetics, Tianjin Key Laboratory of Cellular and Molecular Immunology, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin 300070, China; State Key Laboratory of Molecular Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China; Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Capital Medical University, Beijing 100069, China; Corresponding author
Summary: The histone methyl transferase enhancer of zeste homolog 2 (EZH2) is a master transcriptional regulator involved in histone H3 lysine 27 trimethylation. We aimed to elucidate the precise post-translational regulations of EZH2 and their role in cancer pathogenesis. Here, we show that SET and MYND domain containing 2 (SMYD2) directly methylates EZH2 at lysine 307 (K307) and enhances its stability, which can be relieved by the histone H3K4 demethylase lysine-specific demethylase 1 (LSD1). SMYD2 is critical for EZH2 function in repressing a cohort of genes governing several cancer-associated pathways. In addition, SMYD2 promotes breast cancer cell proliferation, epithelial-mesenchymal transition, and invasion through EZH2 K307 methylation, and it is markedly upregulated in various human cancers. Our data suggest that dynamic crosstalk between SMYD2-mediated EZH2 methylation plays an important role in fine-tuning EZH2 functions in chromatin recruitment and transcriptional repression. : Post-translational modification of proteins is involved in protein stability regulation. Zeng et al. demonstrate that EZH2 K307 is methylated by SMYD2 and demethylated by LSD1. This modification protects EZH2 from degradation. The dynamic crosstalk between SMYD2-mediated EZH2 methylation plays an important role in the transcriptional repression of EZH2. Keywords: methylation, tumorigenesis, breast cancer, EZH2, SMYD2, post-translational modification
