Irradiation of HeLa cells with short-wavelength ultraviolet light (UVC) induces the modification and activation of the preexisting transcription factors c-Fos-c-Jun (AP-1) and TCF/Elk-1, as well as the protein synthesis independent transcriptional activation of the c-fos and c-jun genes. This response to UVC is mediated via obligatory cytoplasmic signal transduction, involving Ras and Raf, Src, and MAP kinases. The UVC response is inhibited by prior down-modulation of growth factor receptor signaling upon growth factor prestimulation, by suramin (an inhibitor of receptor activation) or by expression of a dominant negative epidermal growth factor (EGF) receptor mutant.
View Article and Find Full Text PDFBacteria react to irradiation with short wave length UV (UVC) by mounting a rescuing response which involves the synthesis of proteins engaged in DNA repair, replication and mutagenesis. We analyse here an analogous response shown by mammalian cells in culture and present experimental evidence for the chain of events induced by UV irradiation that leads to enhanced gene expression. Available results suggest that the UV induced signal cascade depends on damage to DNA and also involves components located at the plasma membrane, such as src, ras and raf.
View Article and Find Full Text PDFAdv Enzyme Regul
November 1994
DNA damage inducing treatment of cultured mammalian cells triggers the activation of transcription factors and the prolongation of the half life of p53. As the earliest event detectable in the nucleus (5 min), AP-1 (c-Jun/c-Fos) is post-translationally modified. Triggering this early event and triggering subsequent transcription factor dependent processes requires extra-nuclear components of signal transduction such as Src, Ras, Raf-1 and MAP-2 kinase.
View Article and Find Full Text PDF