期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 112, 期 13, 页码 3985-3990出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1503152112
关键词
posttranslational modification; histone methyltransferase; gene expression
资金
- National Institutes of Health (NIH) [PO1 CA062220]
- NIH [1S10RR031537-01]
Several transcription factors, including p53, NF-kappa B, and STAT3, are modified by the same enzymes that also modify histones, with important functional consequences. We have identified a previously unrecognized dimethylation of K49 of STAT3 that is crucial for the expression of many IL-6-dependent genes, catalyzed by the histone-modifying enzyme enhancer of zeste homolog 2 (EZH2). Loss of EZH2 is protumorigenic in leukemias, but its overexpression is protumorigenic in solid cancers. Connecting EZH2 to a functionally important methylation of STAT3, which is constitutively activated in many tumors, may help reveal the basis of the opposing roles of EZH2 in liquid and solid tumors and also may identify novel therapeutic opportunities.
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