Fos is an essential component of the mammalian UV response.
Mouse 3T3 fibroblasts lacking c-fos were employed to demonstrate an essential function of the UV-inducible transcription factor AP-1 (Fos/Jun) in the response to the cytotoxic effects of short-wavelength ultraviolet (UVC) radiation. Clonogenic survival and proliferation of cells lacking c-fos were drastically reduced following UV irradiation. This UV hypersensitivity manifests itself primarily in increased cell death, partly by apoptosis, and prolonged recovery time from UV-induced cell cycle arrest. Co-culture with wild-type cells did not ameliorate the hypersensitivity of mutant cells. Transcriptional induction of the c-Fos target genes collagenase I, stromelysin-1 and stromelysin-2 by UV is almost absent in cells lacking c-fos which correlates with a reduced UV induction of AP-1 DNA-binding and transactivation activity. The repair of UV-induced DNA lesions was not affected, as shown by unscheduled DNA synthesis and host cell reactivation assays. These data demonstrate that c-Fos is involved in a novel protective function other than DNA repair against the harmful consequences of UVC.
D016475:3T3 Cells; D000818:Animals; D017209:Apoptosis / Q000528:radiation effects; D001483:Base Sequence; D002453:Cell Cycle / Q000528:radiation effects; D002455:Cell Division / Q000528:radiation effects; D004260:DNA Repair / Q000502:physiology; D016762:Genes, fos; D051379:Mice; D008969:Molecular Sequence Data; D009154:Mutation; D018808:Transcription Factor AP-1 / Q000502:physiology* / Q000528:radiation effects; D014466:Ultraviolet Rays
D018808:Transcription Factor AP-1