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PMID: 8265599 Published · ppublish English Journal Article

The mdm-2 gene is induced in response to UV light in a p53-dependent manner.

Perry ME, Piette J, Zawadzki JA, Harvey D, Levine AJ

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.

Related Genes
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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21 references, click to expand
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
Published
1993-12-15
Pages
11623-7
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC48036
Subset
IM
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