STAT3-driven transcription depends upon the dimethylation of K49 by EZH2.
basic_science · Level V
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- Record sourced from PubMed, PMID 25767098.
- Also identified by DOI 10.1073/pnas.1503152112 and PMC identifier 4386339.
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Abstract
Several transcription factors, including p53, NF-κB, 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.
Medical subject headings
- Gene Expression Regulation, Neoplastic
- Polycomb Repressive Complex 2
- STAT3 Transcription Factor