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Phosphorylation of EZH2 by AMPK Suppresses PRC2 Methyltransferase Activity and Oncogenic Function.
Wan, Lixin; Xu, Kexin; Wei, Yongkun; Zhang, Jinfang; Han, Tao; Fry, Christopher; Zhang, Zhao; Wang, Yao Vickie; Huang, Liyu; Yuan, Min; Xia, Weiya; Chang, Wei-Chao; Huang, Wen-Chien; Liu, Chien-Liang; Chang, Yuan-Ching; Liu, Jinsong; Wu, Yun; Jin, Victor X; Dai, Xiangpeng; Guo, Jianfeng; Liu, Jia; Jiang, Shulong; Li, Jin; Asara, John M; Brown, Myles; Hung, Mien-Chie; Wei, Wenyi.
Affiliation
  • Wan L; Department of Molecular Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL 33612, USA; Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA. Electronic address: lixin.wan@moffitt.org.
  • Xu K; Department of Molecular Medicine, University of Texas Health Science Center at San Antonio, San Antonio, TX 78229, USA; Department of Medical Oncology and Center for Functional Cancer Epigenetics, Dana-Farber Cancer Institute, Boston, MA 02215, USA.
  • Wei Y; Department of Molecular and Cellular Oncology, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
  • Zhang J; Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA.
  • Han T; Department of Molecular Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL 33612, USA.
  • Fry C; Cell Signaling Technology, Danvers, MA 01923, USA.
  • Zhang Z; Department of Molecular Medicine, University of Texas Health Science Center at San Antonio, San Antonio, TX 78229, USA.
  • Wang YV; Department of Molecular Medicine, University of Texas Health Science Center at San Antonio, San Antonio, TX 78229, USA.
  • Huang L; Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA; Chinese National Human Genome Center at Shanghai, Shanghai 201203, PRC.
  • Yuan M; Department of Medicine, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA.
  • Xia W; Department of Molecular and Cellular Oncology, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
  • Chang WC; Graduate Institute of Biomedical Sciences and Center for Molecular Medicine, China Medical University, Taichung 404, Taiwan.
  • Huang WC; Department of Surgery, Mackay Memorial Hospital, Taipei, Taiwan.
  • Liu CL; Department of Surgery, Mackay Memorial Hospital, Taipei, Taiwan.
  • Chang YC; Department of Surgery, Mackay Memorial Hospital, Taipei, Taiwan.
  • Liu J; Department of Pathology, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
  • Wu Y; Department of Pathology, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
  • Jin VX; Department of Molecular Medicine, University of Texas Health Science Center at San Antonio, San Antonio, TX 78229, USA.
  • Dai X; Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA.
  • Guo J; Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA; Department of Obstetrics and Gynecology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, PRC.
  • Liu J; Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA; Cardiovascular Research Center, Xi'an Jiaotong University School of Medicine, Xi'an 710061, PRC.
  • Jiang S; Department of Molecular Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL 33612, USA; Department of Oncology, Jining First People's Hospital, Jining, Shandong 272111, PRC; Department of Oncology, Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing 100053,
  • Li J; Department of Molecular Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL 33612, USA; Department of Urology, 254th Hospital of PLA, Tianjin 300142, PRC.
  • Asara JM; Department of Medicine, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA.
  • Brown M; Department of Medical Oncology and Center for Functional Cancer Epigenetics, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA. Electronic address: myles_brown@dfci.harvard.edu.
  • Hung MC; Department of Molecular and Cellular Oncology, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA; Graduate Institute of Biomedical Sciences and Center for Molecular Medicine, China Medical University, Taichung 404, Taiwan. Electronic address: mhung@mdanderson.org.
  • Wei W; Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA. Electronic address: wwei2@bidmc.harvard.edu.
Mol Cell ; 69(2): 279-291.e5, 2018 01 18.
Article in En | MEDLINE | ID: mdl-29351847
Sustained energy starvation leads to activation of AMP-activated protein kinase (AMPK), which coordinates energy status with numerous cellular processes including metabolism, protein synthesis, and autophagy. Here, we report that AMPK phosphorylates the histone methyltransferase EZH2 at T311 to disrupt the interaction between EZH2 and SUZ12, another core component of the polycomb repressive complex 2 (PRC2), leading to attenuated PRC2-dependent methylation of histone H3 at Lys27. As such, PRC2 target genes, many of which are known tumor suppressors, were upregulated upon T311-EZH2 phosphorylation, which suppressed tumor cell growth both in cell culture and mouse xenografts. Pathologically, immunohistochemical analyses uncovered a positive correlation between AMPK activity and pT311-EZH2, and higher pT311-EZH2 correlates with better survival in both ovarian and breast cancer patients. Our finding suggests that AMPK agonists might be promising sensitizers for EZH2-targeting cancer therapies.
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Full text: 1 Database: MEDLINE Main subject: AMP-Activated Protein Kinases / Enhancer of Zeste Homolog 2 Protein Limits: Animals / Female / Humans Language: En Journal: Mol Cell Journal subject: BIOLOGIA MOLECULAR Year: 2018 Type: Article
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Full text: 1 Database: MEDLINE Main subject: AMP-Activated Protein Kinases / Enhancer of Zeste Homolog 2 Protein Limits: Animals / Female / Humans Language: En Journal: Mol Cell Journal subject: BIOLOGIA MOLECULAR Year: 2018 Type: Article