KDM3A histone demethylase functions as an essential factor for activation of JAK2−STAT3 signaling pathwayopen access
- Authors
- Kim H.; Kim D.; Choi S.A.; Kim C.R.; Oh S.K.; Pyo K.E.; Kim J.; Lee S.-H.; Yoon J.-B.; Zhang Y.; Baek S.H.
- Issue Date
- Nov-2018
- Publisher
- National Academy of Sciences
- Keywords
- Histone demethylation; JAK2; KDM3A; Phosphorylation; STAT3
- Citation
- Proceedings of the National Academy of Sciences of the United States of America, v.115, no.46, pp 11766 - 11771
- Pages
- 6
- Indexed
- SCI
SCIE
SCOPUS
- Journal Title
- Proceedings of the National Academy of Sciences of the United States of America
- Volume
- 115
- Number
- 46
- Start Page
- 11766
- End Page
- 11771
- URI
- https://scholarworks.korea.ac.kr/kumedicine/handle/2020.sw.kumedicine/4218
- DOI
- 10.1073/pnas.1805662115
- ISSN
- 0027-8424
1091-6490
- 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. © 2018 National Academy of Sciences. All rights reserved.
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Collections - 1. Basic Science > Department of Biochemistry and Molecular Biology > 1. Journal Articles
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