The Ras-MAPK signal transduction pathway, cancer and chromatin remodeling.
Stimulation of the Ras-mitogen-activated protein 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.
Dunn
Katherine L
KL
Manitoba Institute of Cell Biology, University of Manitoba, 675 McDermot Avenue, Winnipeg, MB R3E 0V9, Canada.
Espino
Paula S
PS
Drobic
Bojan
B
He
Shihua
S
Davie
James R
JR
D000818:Animals; D042002:Chromatin Assembly and Disassembly; D006801:Humans; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D009369:Neoplasms / Q000378:metabolism*; D016283:Proto-Oncogene Proteins p21(ras) / Q000378:metabolism*; D015398:Signal Transduction
D020928:Mitogen-Activated Protein Kinases; D016283:Proto-Oncogene Proteins p21(ras)