Abstract
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.
MeSH Terms
3T3 Cells
Animals
Cells, Cultured
Chloramphenicol O-Acetyltransferase/biosynthesis
Colony-Forming Units Assay
DNA Replication/radiation effects
Dose-Response Relationship, Radiation
Gene Expression/radiation effects
Genes, p53/radiation effects
Kinetics
Mice
Mice, Inbred BALB C
Neoplasm Proteins/biosynthesis
Nuclear Proteins
Proto-Oncogene Proteins
Proto-Oncogene Proteins c-mdm2
Time Factors
Transcription, Genetic
Transfection
Tumor Suppressor Protein p53/biosynthesis,metabolism
Ultraviolet Rays
Chemicals
Neoplasm Proteins
Nuclear Proteins
Proto-Oncogene Proteins
Tumor Suppressor Protein p53
Chloramphenicol O-Acetyltransferase
Mdm2 protein, mouse
Proto-Oncogene Proteins c-mdm2
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Perry M E
Department of Molecular Biology, Princeton University, NJ 08544-1014.
Piette J
Zawadzki J A
Harvey D
Levine A J
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