查看文章

We have previously shown that the persistent activation of p42/p44^MAPK is required to pass the G₁ restriction point in fibroblasts (Pagès, G., Lenormand, P., L'Allemain, G., Chambard, J. C., Meloche, S., and Pouysségur, J. (1993) Proc. Natl. Acad. Sci. U. S. A. 90, 8319-8323) and postulated that MAPKs control the activation of G₁ cyclin-dependent complexes. We examined the mitogen-dependent induction of cyclin D1 expression, one of the earliest cell cycle-related events to occur during the G₀/G₁ to S-phase transition, as a potential target of MAPK regulation. Effects exerted either by the p42/p44^MAPK or the p38/HOG^MAPK cascade on the regulation of cyclin D1 promoter activity or cyclin D1 expression were compared in CCL39 cells, using a co-transfection procedure. We found that inhibition of the p42/p44^MAPK signaling by expression of dominant-negative forms of either mitogen-activated protein kinase …