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Updated: Aug 19, 2026

An Integrated Platform for Genome-wide Mapping of Chromatin States Using High-throughput ChIP-sequencing in Tumor Tissues
10:41

An Integrated Platform for Genome-wide Mapping of Chromatin States Using High-throughput ChIP-sequencing in Tumor Tissues

Published on: April 5, 2018

The Ras-MAPK signal transduction pathway, cancer and chromatin remodeling

Katherine L Dunn1, Paula S Espino, Bojan Drobic

  • 1Manitoba Institute of Cell Biology, University of Manitoba, 675 McDermot Avenue, Winnipeg, MB R3E 0V9, Canada.

Biochemistry and Cell Biology = Biochimie Et Biologie Cellulaire
|March 5, 2005
PubMed

Insights

The Ras-MAPK pathway regulates gene expression via histone modification. Aberrant pathway activation in cancer, particularly breast cancer, leads to altered chromatin structure and gene transcription.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Cancer Biology

Background:

  • The Ras-mitogen-activated protein kinase (MAPK) pathway controls immediate-early gene expression (c-fos, c-myc).
  • Mitogen- and stress-activated protein kinases (MSK) 1 and 2 are downstream effectors, acting as histone H3 kinases.
  • MSK1/2 activity and histone H3 phosphorylation are implicated in chromatin remodeling and gene transcription.

Purpose of the Study:

  • To review the deregulation of the Ras-MAPK pathway in cancer, focusing on breast cancer.
  • To discuss the roles of MSK1 and MSK2 in this context.
  • To explore the impact of a constitutively active Ras-MAPK pathway on chromatin remodeling and gene expression.

Main Methods:

  • Review of existing literature on Ras-MAPK signaling, MSK kinases, and cancer.
  • Analysis of chromatin immunoprecipitation assay data linking histone phosphorylation to immediate-early genes.
  • Examination of chromatin structure changes in oncogene-transformed cells with active Ras-MAPK signaling.

Main Results:

  • Mitogen-induced histone H3 phosphorylation is associated with immediate-early genes.
  • MSK1/2 activity and H3 phosphorylation are crucial for chromatin remodeling and transcription.
  • Constitutive Ras-MAPK activation in cancer cells increases histone H1/H3 phosphorylation and relaxes chromatin structure.

Conclusions:

  • Deregulation of the Ras-MAPK pathway significantly impacts chromatin remodeling and gene expression in cancer.
  • MSK1/2 play a critical role in mediating these effects.
  • Understanding these mechanisms is vital for developing targeted breast cancer therapies.

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