The mammalian UV response: c-Jun induction is required for exit from p53-imposed growth arrest.
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.
Shaulian
E
E
Laboratory of Gene Regulation and Signal Transduction University of California, San Diego 9500 Gilman Drive 92093, La Jolla, CA, USA.
Schreiber
M
M
Piu
F
F
Beeche
M
M
Wagner
E F
EF
Karin
M
M
D000818:Animals; D002453:Cell Cycle; D002460:Cell Line; D002470:Cell Survival; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D004247:DNA / Q000096:biosynthesis / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000378:metabolism; D005347:Fibroblasts; D005786:Gene Expression Regulation; D017930:Genes, Reporter; D016758:Genes, jun / Q000235:genetics*; D006801:Humans; D051379:Mice; D015398:Signal Transduction; D014158:Transcription, Genetic / Q000235:genetics; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*; D014466:Ultraviolet Rays
C493956:CDKN1A protein, human; C493957:Cdkn1a protein, mouse; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D004791:Enzyme Inhibitors; D016159:Tumor Suppressor Protein p53; D004247:DNA