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Science 310 (5746): 306-310

Copyright © 2005 by the American Association for the Advancement of Science

Akt-Mediated Phosphorylation of EZH2 Suppresses Methylation of Lysine 27 in Histone H3

Tai-Lung Cha,1,2* Binhua P. Zhou,1{dagger} Weiya Xia,1 Yadi Wu,1 Cheng-Chieh Yang,1,2 Chun-Te Chen,1 Bo Ping,1 Arie P. Otte,3 Mien-Chie Hung1,2{ddagger}

Abstract: Enhancer of Zeste homolog 2 (EZH2) is a methyltransferase that plays an important role in many biological processes through its ability to trimethylate lysine 27 in histone H3. Here, we show that Akt phosphorylates EZH2 at serine 21 and suppresses its methyltransferase activity by impeding EZH2 binding to histone H3, which results in a decrease of lysine 27 trimethylation and derepression of silenced genes. Our results imply that Akt regulates the methylation activity, through phosphorylation of EZH2, which may contribute to oncogenesis.

1 Department of Molecular and Cellular Oncology, the University of Texas M. D. Anderson Cancer Center, Houston, TX 77030, USA.
2 Graduate School of Biomedical Sciences, the University of Texas Health Science Center at Houston, Houston, TX 77030, USA.
3 Swammerdam Institute for Life Sciences, University of Amsterdam, Kruislaan 406, 1098 SM Amsterdam, the Netherlands.

* Present address: Division of Urology, Department of Surgery, Tri-Service General Hospital, National Defense Medical Center, National Defense University, Taipei, 104, Taiwan.

{dagger} Present address: Sealy Center for Cancer Cell Biology, the University of Texas Medical Branch, Galveston, TX 77555–1048, USA.

{ddagger} To whom correspondence should be addressed. E-mail: mhung{at}

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