ULTRAVIOLET-RADIATION, BUT NOT GAMMA-RADIATION OR ETOPOSIDE-INDUCED DNA-DAMAGE, RESULTS IN THE PHOSPHORYLATION OF THE MURINE P53 PROTEIN ATSERINE-389

Polyclonal antibodies were produced and purified that selectively reac t with a p53 epitope containing the murine phosphoserine-389 or the hu man phosphoserine-392 residue, but not the unphosphorylated epitope, T hese antibodies, termed alpha 392, were employed to demonstrate that t he phosphorylation of this serine-389 residue in the p53 protein occur s in vivo in response to ultraviolet radiation of cells containing the p53 protein. After ultraviolet radiation of cells in culture, p53 lev els increase and concomitantly serine-389 is phosphorylated in these c ells. By contrast, the serine-389 phosphorylation of the p53 protein w as not detected by these antibodies in the increased levels of p53 pro tein made in response to gamma radiation or the treatment of cells wit h etoposide. These results demonstrate an ultraviolet responsive and s pecific phosphorylation site at serine-389 of the mouse or serine-392 of the human p53 protein. Previous studies have demonstrated that this phosphorylation of p53 activates the protein for specific DNA binding . This study demonstrates in vivo a unique phosphorylation site in the p53 protein that responds to a specific type of DNA damage.