Stimulation of the Ras-MAPK pathway leads to independent phosphorylation of histone H3 on serine 10 and 28
- PMID: 15735677
- DOI: 10.1038/sj.onc.1208521
Stimulation of the Ras-MAPK pathway leads to independent phosphorylation of histone H3 on serine 10 and 28
Abstract
The Ras-mitogen activated protein kinase (Ras-MAPK) pathway plays an integral role in the formation of human malignancies. Stimulation of this pathway results in phosphorylation of histone H3 at serines 10 and 28 and expression of immediate-early genes. Phosphorylated (serine 10) H3, which is also acetylated on lysine 14, is associated with immediate-early genes. In this report, we investigated the relationship between these two H3 phosphorylation events in parental and ras-transformed fibroblasts. Immunoblot analyses of two-dimensional gel patterns demonstrated that all three H3 variants were phosphorylated after stimulation of the Ras-MAPK pathway and during mitosis. Following stimulation of the Ras-MAPK pathway, H3 phosphorylated on serines 10 and 28 was excluded from regions of highly condensed chromatin and was present in increased levels in ras-transformed cells. Although H3 phosphorylated at serine 10 or 28 was dynamically acetylated, H3 phosphorylated at serine 28 had a higher steady state of acetylation than that of H3 phosphorylated at serine 10. When visualized with indirect immunofluorescence, most foci of phosphorylated serine 28 H3 did not co-localize with foci of H3 phosphorylated on serine 10 or phosphoacetylated on serine 10 and lysine 14, suggesting that these two phosphorylation events act separately to promote gene expression.
Similar articles
-
Increased genomic instability and altered chromosomal protein phosphorylation timing in HRAS-transformed mouse fibroblasts.Genes Chromosomes Cancer. 2009 May;48(5):397-409. doi: 10.1002/gcc.20649. Genes Chromosomes Cancer. 2009. PMID: 19191262
-
Ser-10 phosphorylation of histone H3 and immediate early gene expression in oncogene-transformed mouse fibroblasts.Cancer Res. 2002 Jan 1;62(1):75-8. Cancer Res. 2002. PMID: 11782362
-
The Ras-MAPK signal transduction pathway, cancer and chromatin remodeling.Biochem Cell Biol. 2005 Feb;83(1):1-14. doi: 10.1139/o04-121. Biochem Cell Biol. 2005. PMID: 15746962 Review.
-
Phosphorylation at serine 28 and acetylation at lysine 9 of histone H3 induced by trichostatin A.Oncogene. 2003 Aug 14;22(34):5291-7. doi: 10.1038/sj.onc.1206507. Oncogene. 2003. PMID: 12917630
-
Phosphorylation of serine 10 in histone H3, what for?J Cell Sci. 2003 Sep 15;116(Pt 18):3677-85. doi: 10.1242/jcs.00735. J Cell Sci. 2003. PMID: 12917355 Review.
Cited by
-
Molecular mechanisms insulating proliferation from genotoxic stress in B lymphocytes.Trends Immunol. 2023 Sep;44(9):668-677. doi: 10.1016/j.it.2023.06.010. Epub 2023 Aug 10. Trends Immunol. 2023. PMID: 37573227 Free PMC article. Review.
-
Mutation of histone H3 serine 28 to alanine influences H3K27me3-mediated gene silencing in Arabidopsis thaliana.Plant Physiol. 2022 Nov 28;190(4):2417-2429. doi: 10.1093/plphys/kiac409. Plant Physiol. 2022. PMID: 36053193 Free PMC article.
-
IER2-induced senescence drives melanoma invasion through osteopontin.Oncogene. 2021 Nov;40(47):6494-6512. doi: 10.1038/s41388-021-02027-6. Epub 2021 Oct 5. Oncogene. 2021. PMID: 34611309 Free PMC article.
-
Programmable human histone phosphorylation and gene activation using a CRISPR/Cas9-based chromatin kinase.Nat Commun. 2021 Feb 9;12(1):896. doi: 10.1038/s41467-021-21188-2. Nat Commun. 2021. PMID: 33563994 Free PMC article.
-
Megakaryocytes contain extranuclear histones and may be a source of platelet-associated histones during sepsis.Sci Rep. 2020 Mar 12;10(1):4621. doi: 10.1038/s41598-020-61309-3. Sci Rep. 2020. PMID: 32165642 Free PMC article.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Molecular Biology Databases