| Literature DB >> 30377265 |
Hyunkyung Kim1, Dongha Kim1, Seon Ah Choi1, Chang Rok Kim1, Se Kyu Oh1, Ki Eun Pyo1, Joomyung Kim1, Seung-Hoon Lee2, Jong-Bok Yoon2, Yi Zhang3, Sung Hee Baek4.
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.Entities:
Keywords: JAK2; KDM3A; STAT3; histone demethylation; phosphorylation
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Year: 2018 PMID： 30377265 PMCID： PMC6243239 DOI： 10.1073/pnas.1805662115
Source DB: PubMed Journal: Proc Natl Acad Sci U S A ISSN： 0027-8424 Impact factor: 11.205