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KDM3A histone demethylase functions as an essential factor for activation of JAK2-STAT3 signaling pathway.
- Source :
-
Proceedings of the National Academy of Sciences of the United States of America [Proc Natl Acad Sci U S A] 2018 Nov 13; Vol. 115 (46), pp. 11766-11771. Date of Electronic Publication: 2018 Oct 30. - Publication Year :
- 2018
-
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.<br />Competing Interests: The authors declare no conflict of interest.
- Subjects :
- Epigenesis, Genetic
HEK293 Cells metabolism
HeLa Cells
Histones metabolism
Humans
Interleukin-6 metabolism
Janus Kinase 2 metabolism
Jumonji Domain-Containing Histone Demethylases genetics
Phosphorylation
Protein-Tyrosine Kinases metabolism
STAT3 Transcription Factor metabolism
Signal Transduction
Transcriptional Activation
Jumonji Domain-Containing Histone Demethylases metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1091-6490
- Volume :
- 115
- Issue :
- 46
- Database :
- MEDLINE
- Journal :
- Proceedings of the National Academy of Sciences of the United States of America
- Publication Type :
- Academic Journal
- Accession number :
- 30377265
- Full Text :
- https://doi.org/10.1073/pnas.1805662115