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

Research output: Contribution to journalArticle

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

Fingerprint

Histone Demethylases
TYK2 Kinase
Janus Kinase 2
STAT3 Transcription Factor
Epigenomics
Enzyme Activation
Histones
Methylation
Lysine
Tyrosine
Interleukin-6
Homeostasis
Phosphorylation

All Science Journal Classification (ASJC) codes

  • General

Cite this

Kim, Hyunkyung ; Kim, Dongha ; Choi, Seon Ah ; Kim, Chang Rok ; Oh, Se Kyu ; Pyo, Ki Eun ; Kim, Joomyung ; Lee, Seung Hoon ; Yoon, Jong Bok ; Zhang, Yi ; Baek, Sung Hee. / KDM3A histone demethylase functions as an essential factor for activation of JAK2-STAT3 signaling pathway. In: Proceedings of the National Academy of Sciences of the United States of America. 2018 ; Vol. 115, No. 46. pp. 11766-11771.
@article{97ee41e4a56b42798a7ac000c2d3f232,
title = "KDM3A histone demethylase functions as an essential factor for activation of JAK2-STAT3 signaling pathway",
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.",
author = "Hyunkyung Kim and Dongha Kim and Choi, {Seon Ah} and Kim, {Chang Rok} and Oh, {Se Kyu} and Pyo, {Ki Eun} and Joomyung Kim and Lee, {Seung Hoon} and Yoon, {Jong Bok} and Yi Zhang and Baek, {Sung Hee}",
year = "2018",
month = "11",
day = "13",
doi = "10.1073/pnas.1805662115",
language = "English",
volume = "115",
pages = "11766--11771",
journal = "Proceedings of the National Academy of Sciences of the United States of America",
issn = "0027-8424",
number = "46",

}

KDM3A histone demethylase functions as an essential factor for activation of JAK2-STAT3 signaling pathway. / Kim, Hyunkyung; Kim, Dongha; Choi, Seon Ah; Kim, Chang Rok; Oh, Se Kyu; Pyo, Ki Eun; Kim, Joomyung; Lee, Seung Hoon; Yoon, Jong Bok; Zhang, Yi; Baek, Sung Hee.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 115, No. 46, 13.11.2018, p. 11766-11771.

Research output: Contribution to journalArticle

TY - JOUR

T1 - KDM3A histone demethylase functions as an essential factor for activation of JAK2-STAT3 signaling pathway

AU - Kim, Hyunkyung

AU - Kim, Dongha

AU - Choi, Seon Ah

AU - Kim, Chang Rok

AU - Oh, Se Kyu

AU - Pyo, Ki Eun

AU - Kim, Joomyung

AU - Lee, Seung Hoon

AU - Yoon, Jong Bok

AU - Zhang, Yi

AU - Baek, Sung Hee

PY - 2018/11/13

Y1 - 2018/11/13

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=85056489115&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85056489115&partnerID=8YFLogxK

U2 - 10.1073/pnas.1805662115

DO - 10.1073/pnas.1805662115

M3 - Article

C2 - 30377265

AN - SCOPUS:85056489115

VL - 115

SP - 11766

EP - 11771

JO - Proceedings of the National Academy of Sciences of the United States of America

JF - Proceedings of the National Academy of Sciences of the United States of America

SN - 0027-8424

IS - 46

ER -