The mammalian UV response: c-Jun induction is required for exit from p53-imposed growth arrest

Eitan Shaulian, Martin Schreiber, Fabrice Piu, Michelle Beeche, Erwin F. Wagner, Michael Karin*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

258 Scopus citations

Abstract

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.

Original languageAmerican English
Pages (from-to)897-908
Number of pages12
JournalCell
Volume103
Issue number6
DOIs
StatePublished - 2000
Externally publishedYes

Bibliographical note

Funding 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.

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