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    Science. 2005 Oct 14;310(5746):306-10.

    Akt-mediated phosphorylation of EZH2 suppresses methylation of lysine 27 in histone H3.

    Cha TL, Zhou BP, Xia W, Wu Y, Yang CC, Chen CT, Ping B, Otte AP, Hung MC.

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    Department of Molecular and Cellular Oncology, the University of Texas M. D. Anderson Cancer Center, Houston, TX 77030, USA.

    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.

    PMID:
    16224021
    [PubMed - indexed for MEDLINE]

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