The mammalian UV response results in rapid and dramatic induction of c-jun. Induction of a protooncogene, normally involved in mitogenic responses, by a genotoxic agent that causes growth arrest seems paradoxical. We now provide an explanation for the role of c-Jun in the UV response of mouse fibroblasts. c-Jun is necessary for cell-cycle reentry of UV-irradiated cells, but does not participate in the response to ionizing radiation. Cells lacking c-Jun undergo prolonged cell-cycle arrest, but resist apoptosis, whereas cells that express c-Jun constitutively do not arrest and undergo apoptosis. This function of c-Jun is exerted through negative regulation of p53 association with the p21 promoter. Cells lacking c-Jun exhibit prolonged p21 induction, whereas constitutive c-Jun inhibits UV-mediated p21 induction.
Bibliographical noteFunding Information:
We thank A. Haghigi and R. A. Gjerset for measurement of DNA repair rates; J. Aguilera for help with IR; M. Kapoor and G. Lozano for the anti-phospho 389 antibody; and T. Hunter and G. Wahl for critical reading of the manuscript. Research was supported by grants from the NIH (CA76188), the DOE (DE-FG03-86ER60429), and the State of California Cancer Research Program (99-00529V-10249) to M. K. M. K. is the Frank and Else Schilling-American Cancer Society Research Professor.