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

Katherine L Dunn, Paula S Espino, Bojan Drobic, Shihua He, James R Davie

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

Biochemistry and cell biology = Biochimie et biologie cellulaire 2005 Feb

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Stimulation of the Ras-mitogen-activated prot ein kinase (MAPK) signal transduction pathway results in a multitude of events including expression of the immediate-early genes, c-fos and c-myc. Downstream targets of this stimulated pathway are the mitogen- and stress-activated protein kinases (MSK) 1 and 2, which are histone H3 kinases. In chromatin immunoprecipitation assays, it has been shown that the mitogen-induced phosphorylated H3 is associated with the immediate-early genes and that MSK1/2 activity and H3 phosphorylation have roles in chromatin remodeling and transcription of these genes. In oncogene-transformed fibroblasts in which the Ras-MAPK pathway is constitutively active, histone H1 and H3 phosphorylation is increased and the chromatin of these cells has a more relaxed structure than the parental cells. In this review we explore the deregulation of the Ras-MAPK pathway in cancer, with an emphasis on breast cancer. We discuss the features of MSK1 and 2 and the impact of a constitutively activated Ras-MAPK pathway on chromatin remodeling and gene expression.

Citation

Katherine L Dunn, Paula S Espino, Bojan Drobic, Shihua He, James R Davie. The Ras-MAPK signal transduction pathway, cancer and chromatin remodeling. Biochemistry and cell biology = Biochimie et biologie cellulaire. 2005 Feb;83(1):1-14