p21ras in carcinogenesis.
The activation of p21ras proteins is required in signal transduction pathways that lead to cell proliferation. More recently, a role for p21ras proteins has also been suggested in pathways to apoptosis and in the regulation of the cell cycle. Pointmutated p21ras oncogenes code for constitutively activated p21ras proteins, which disturb the balance between cell growth and cell death in favour of cell growth. In this way, p21ras oncoproteins may contribute to carcinogenesis. The binding of growth factors to their receptors triggers a cascade of protein interactions, including activation of the p21ras proteins. In turn, p21ras proteins set the machinery for cell division in motion by stimulating different effector proteins which regulate the morphological alterations, the nutritional requirements, and the changes in gene expression necessary for cell division. The presence of p21ras oncoproteins constitutively stimulate proliferation, whilst the apoptotic pathway is suppressed along with the loss of cell cycle regulation. This review describes the function of the p21ras proteins in signal transduction pathways that control proliferation and apoptosis, and regulate the cell cycle. The dysregulation of these signal transduction pathways due to the presence of p21ras oncoproteins is discussed in the context of early carcinogenesis.
de Vries
J E
JE
Department of Physiology, University of Limburg, Maastricht, The Netherlands.
ten Kate
J
J
Bosman
F T
FT
D000818:Animals; D002273:Carcinogens / Q000032:analysis*; D002471:Cell Transformation, Neoplastic / Q000187:drug effects*; D004249:DNA Damage / Q000187:drug effects*; D006801:Humans; D016283:Proto-Oncogene Proteins p21(ras) / Q000235:genetics* / Q000494:pharmacology*
D002273:Carcinogens; C501009:HRAS protein, human; D016283:Proto-Oncogene Proteins p21(ras)