c-fos and Growth Control

Abstract

It is now generally accepted that the normal cellular homologues of retroviral oncogenes, the proto-oncogenes, may have crucial physiological functions in the regulation of cellular proliferation. This hypothesis is strongly supported by the observation that three proto-oncogenes, c-sis, c-erbB and c-fms are part of the cellular growth factor-receptor system (Doolittle et al. 1983, Waterfield et al. 1985, Downward et al. 1984, Sherr et al. 1985). In addition, expression of proto-oncogenes encoding nuclear proteins has been shown to increase rapidly following the stimulation of different cell types using several mitogenic agents: The transient transcriptional activation of the c-fos gene is followed by the accumulation of c-myc RNA (Kelly et al. 1983, Greenberg and Ziff 1984, Cochran et al. 1984, Kruijer et al. 1984, Miiller et al. 1984). This article summarizes the available data suggesting an early role for c-fos in inducing the “competent state” in fibroblasts and thus in the movement of quiescent cells into the cell cycle. In addition, we will discuss the signal transduction pathways that seem to be involved in the induction of c-fos by growth factors.