Proceedings of the National Academy of Sciences · 1993 · 248 citations · 23 references
Uv-stimulated Mdm-2 ExpressionGenome InstabilityP53-dependent MannerMdm-2 InductionPhotocarcinogenesisPhototoxicityMolecular BiologyCancer Cell BiologyMdm-2 ExpressionMdm-2 GeneTumor SuppressorCancer GeneticsMedicineCell BiologyCancer ResearchTumor MicroenvironmentTumor BiologyUv Light
Irradiation of mammalian cells with UV light results in a dose-dependent accumulation of the p53 tumor-suppressor gene product that is evident within 2 hr. UV treatment causes a dramatic increase in p53-specific transcriptional transactivation activity and an increase in expression of the p53-responsive gene mdm-2. UV-stimulated mdm-2 expression is not directly correlated with the level of p53 protein in a cell because mdm-2 induction is delayed at high UV doses even though p53 levels rise almost immediately. Cells lacking p53 protein do not respond to UV by increasing their expression of mdm-2. The delayed induction of mdm-2 at high UV doses suggests that, in addition to p53 protein levels, other factors contribute to the regulation of mdm-2 expression following UV treatment. The time of induction of mdm-2 in cells treated with UV light correlates with recovery of normal rates of DNA synthesis, presumably after DNA repair. These data indicate a possible role for mdm-2 in cell cycle progression.
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The p53-mdm-2 autoregulatory feedback loop.
J. Henri Bayle, David C. Olson, Arnold J. Levine · Genes & Development · 1993 · 1.8K citations · Full text
mdm2 expression is induced by wild type p53 activity.
Yaacov Barak, T. Juven, Rebecca Haffner et al. · The EMBO Journal · 1993 · 1.3K citations · Full text