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Application of MassSQUIRM for Quantitative Measurements of Lysine Demethylase Activity
07:02

Application of MassSQUIRM for Quantitative Measurements of Lysine Demethylase Activity

Published on: March 11, 2012

13.8K

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

Hyunkyung Kim1, Dongha Kim1, Seon Ah Choi1

  • 1Creative Research Initiatives Center for Epigenetic Code and Diseases, Department of Biological Sciences, Seoul National University, 08826 Seoul, South Korea.

Proceedings of the National Academy of Sciences of the United States of America
|November 1, 2018
PubMed

Insights

Lysine-specific demethylase 3A (KDM3A) activates the Janus tyrosine kinase 2 (JAK2)-signal transducer and activator of transcription 3 (STAT3) pathway. Inhibiting KDM3A phosphorylation offers a potential therapeutic strategy for cancers driven by this pathway.

Area of Science:

  • Epigenetics
  • Molecular Biology
  • Cancer Biology

Background:

  • The Janus tyrosine kinase 2 (JAK2)-signal transducer and activator of transcription 3 (STAT3) signaling pathway is crucial for cellular functions.
  • Dysregulation of this pathway is linked to various human cancers.

Purpose of the Study:

  • To investigate the role of lysine-specific demethylase 3A (KDM3A) in the JAK2-STAT3 signaling pathway.
  • To elucidate the mechanistic link between KDM3A and JAK2-STAT3 activation in cancer.

Main Methods:

  • Investigated KDM3A's function as an epigenetic enzyme.
  • Examined KDM3A phosphorylation by JAK2.
  • Analyzed the impact of the JAK2-KDM3A cascade on histone H3K9 methylation.
  • Studied the role of KDM3A in STAT3-dependent transcription.

Main Results:

  • KDM3A acts as an essential epigenetic enzyme activating the JAK2-STAT3 pathway.
  • KDM3A is tyrosine-phosphorylated by JAK2 and functions as a STAT3 transcriptional coactivator.
  • The JAK2-KDM3A signaling cascade, induced by IL-6, alters histone H3K9 methylation, linking epigenetic control to pathway activation.

Conclusions:

  • KDM3A is a key regulator of the JAK2-STAT3 signaling pathway.
  • Inhibition of KDM3A phosphorylation presents a potential therapeutic approach against cancers involving the JAK2-STAT3 pathway.
Keywords:
JAK2KDM3ASTAT3histone demethylationphosphorylation

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