STAT3-driven transcription depends upon the dimethylation of K49 by EZH2
M Dasgupta, JKT Dermawan… - Proceedings of the …, 2015 - National Acad Sciences
M Dasgupta, JKT Dermawan, B Willard, GR Stark
Proceedings of the National Academy of Sciences, 2015•National Acad SciencesSeveral 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 …
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 …
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.
National Acad Sciences