Related Experiment Video

Updated: Oct 3, 2026

Expression Analysis of Mammalian Linker-histone Subtypes
14:40

Expression Analysis of Mammalian Linker-histone Subtypes

Published on: March 19, 2012

Ser-10 phosphorylation of histone H3 and immediate early gene expression in oncogene-transformed mouse fibroblasts

Ileana S Strelkov1, James R Davie

  • 1Manitoba Institute of Cell Biology, Winnipeg, Manitoba, R3E 0V9 Canada.

Cancer Research
|January 10, 2002
PubMed

Insights

MSK1, not Rsk-2, phosphorylates histone H3 upon Ras-MAPK pathway activation. MSK1 inhibition blocks gene expression changes linked to oncogenic transformation.

Area of Science:

  • Cellular signaling
  • Molecular biology
  • Epigenetics

Background:

  • The Ras-mitogen-activated protein kinase (MAPK) pathway regulates cell growth and differentiation.
  • Histone H3 phosphorylation is a key epigenetic modification influenced by this pathway.
  • Rsk-2 and MSK1 are known kinases activated by Ras-MAPK signaling.

Purpose of the Study:

  • To determine which kinase, Rsk-2 or MSK1, mediates histone H3 phosphorylation induced by 12-O-tetradecanoylphorbol-13-acetate (TPA).
  • To investigate the role of MSK1 in TPA-induced gene expression in mouse fibroblasts.

Main Methods:

  • Utilized Rsk-2 and MSK1 specific inhibitors in 10T(1/2) and H-ras-transformed Ciras-3 mouse fibroblasts.
  • Performed in vitro kinase assays to assess Rsk-2 and MSK1 activity.
  • Measured gene expression of c-fos and urokinase plasminogen activator following TPA treatment and MSK1 inhibition.

Main Results:

  • MSK1 was identified as the primary kinase responsible for TPA-induced histone H3 phosphorylation.
  • Rsk-2 was found to phosphorylate histone H2B, but not H3, in vitro.
  • Inhibition of MSK1 with H89 blocked TPA-induced H3 phosphorylation and reduced c-fos and urokinase plasminogen activator gene expression.

Conclusions:

  • MSK1 is the key mediator of histone H3 phosphorylation downstream of the Ras-MAPK pathway in response to TPA.
  • Aberrant activation of the Ras-MAPK pathway and MSK1 may contribute to altered gene expression in oncogene-transformed cells.
  • Targeting MSK1 could offer a strategy to modulate gene expression in cancer contexts.

More Related Videos

Chromatin Immunoprecipitation Assay for Tissue-specific Genes using Early-stage Mouse Embryos11:02

Chromatin Immunoprecipitation Assay for Tissue-specific Genes using Early-stage Mouse Embryos

Published on: April 29, 2011

Chromatin Immunoprecipitation (ChIP) to Assay Dynamic Histone Modification in Activated Gene Expression in Human Cells13:20

Chromatin Immunoprecipitation (ChIP) to Assay Dynamic Histone Modification in Activated Gene Expression in Human Cells

Published on: July 29, 2010

Related Concept Videos

TGF - β Signaling Pathway01:16

TGF - β Signaling Pathway

The TGF-β signaling pathway regulates cell growth, differentiation, adhesion, motility, and development. TGF-β ligands that induce TGF-β signaling are synthesized in their latent form. Several proteases or cell surface receptors such as integrins act upon the latent form, releasing the active ligand. There are three types of mammalian TGF-βs: (TGF-β1, TGF-β2, and TGF-β3) that bind as homodimers or heterodimers to TGF-β receptors. The TGF-β receptors are of three kinds RI, RII, and RIII. The RI...
Histone Modification02:32

Histone Modification

The histone proteins have a flexible N-terminal tail extending out from the nucleosome. These histone tails are often subjected to post-translational modifications such as acetylation, methylation, phosphorylation, and ubiquitination. Particular combinations of these modifications form “histone codes” that influence the chromatin folding and tissue-specific gene expression.
Acetylation
The enzyme histone acetyltransferase adds acetyl group to the histones. Another enzyme, histone deacetylase,...
MAPK Signaling Cascades01:07

MAPK Signaling Cascades

Mitogen-activated protein kinase, or MAPK pathway, activates three sequential kinases to regulate cellular responses such as proliferation, differentiation, survival, and apoptosis. The canonical MAPK pathway starts with a mitogen or growth factor binding to an RTK. The activated RTKs stimulate Ras, which recruits Raf or MAP3 Kinase (MAPKKK), the first kinase of the MAPK signaling cascade. Raf further phosphorylates and activates MEK or MAP2 Kinases (MAPKK), which in turn phosphorylates MAP...
PI3K/mTOR/AKT Signaling Pathway01:22

PI3K/mTOR/AKT Signaling Pathway

The mammalian target of rapamycin  (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1  (mTORC1) and mTOR complex 2  (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast,  mTORC2 consists of a rapamycin-insensitive companion...
Somatic to iPS Cell Reprogramming01:29

Somatic to iPS Cell Reprogramming

Reprogramming alters the gene expression in somatic cells, transforming them into induced pluripotent stem (iPS) cells over several generations. Scientists can reprogram cells by introducing genes for four transcription factors—Oct4, Sox2, Klf4, and c-Myc (OSKM) by viral or non-viral methods. These factors are also known as Yamanaka factors after Shinya Yamanaka, who first generated iPS cells using mouse skin cells. Yamanaka was awarded the Nobel Prize in Physiology or Medicine in 2012 for this...
Cell Specific Gene Expression01:58

Cell Specific Gene Expression

Multicellular organisms contain a variety of structurally and functionally distinct cell types, but the DNA in all the cells originated from the same parent cells. The differences in the cells can be attributed to the differential gene expression. Liver cells, whose functions include detoxification of blood, production of bile to metabolize fats, and synthesis of proteins essential for metabolism, must express a specific set of genes to perform their functions. Gene expression also varies with...