KDM3A histone demethylase functions as an essential factor for activation of JAK2-STAT3 signaling pathway

Hyunkyung Kim, Dongha Kim, Seon Ah Choi, Chang Rok Kim, Se Kyu Oh, Ki Eun Pyo, Joomyung Kim, Seung Hoon Lee, Jong Bok Yoon, Yi Zhang, Sung Hee Baek

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5 Citations (Scopus)

Abstract

Janus tyrosine kinase 2 (JAK2)-signal transducer and activator of transcription 3 (STAT3) signaling pathway is essential for modulating cellular development, differentiation, and homeostasis. Thus, dysregulation of JAK2-STAT3 signaling pathway is frequently associated with human malignancies. Here, we provide evidence that lysine-specific demethylase 3A (KDM3A) functions as an essential epigenetic enzyme for the activation of JAK2-STAT3 signaling pathway. KDM3A is tyrosine-phosphorylated by JAK2 in the nucleus and functions as a STAT3-dependent transcriptional coactivator. JAK2-KDM3A signaling cascade induced by IL-6 leads to alteration of histone H3K9 methylation as a predominant epigenetic event, thereby providing the functional and mechanistic link between activation of JAK2-STAT3 signaling pathway and its epigenetic control. Together, our findings demonstrate that inhibition of KDM3A phosphorylation could be a potent therapeutic strategy to control oncogenic effect of JAK2-STAT3 signaling pathway.

Original languageEnglish
Pages (from-to)11766-11771
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume115
Issue number46
DOIs
Publication statusPublished - 2018 Nov 13

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