DNA damaging agents and growth factors induce changes in the program of expressed gene products through common routes

There is good reason to believe that the different kinds of skin cancer are promoted by exposure to sunlight, most notably to the ultraviolet (UV) part of its spectrum. This paper reviews recent data from our laboratory that address the mechanism of the induced changes. How does a DNA damaging agent such as short wave length UV (UVC) elicit changes of transcription (in the case of the c-fos, c-jun and the collagenase gene) and of protein half life (in the case of p53)? In an attempt to determine conditions for the p53 stabilization, we came across an interesting observation. The p53 turnover appears to be under dual control: the half life of the protein in influenced by treatment of cells with the DNA damaging agent and by the level of preexisting p53. The initial events triggered by the DNA damaging agents depend, in our hands, on the presence of the cell nucleus, but nevertheless involve a signal transduction cascade that is shared by growth factors and that includes growth factor receptors and cytoplasmic GTP-binding proteins as well as protein kinases.