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PMID: 8570655 Published · ppublish English Journal Article Research Support, U.S. Gov't, P.H.S.

Transcriptional activation of the human proliferating-cell nuclear antigen promoter by p53.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 93 ·No. 2 ·1996-01-23 ·Pages 895-9

Morris GF, Bischoff JR, Mathews MB

Abstract

Proliferating-cell nuclear antigen (PCNA) is a DNA damage-inducible protein that performs an essential function in DNA replication and repair as an auxiliary factor for DNA polymerases delta and epsilon. Examination of the human PCNA promoter DNA sequence revealed a site with homology to the consensus DNA sequence bound by p53. PCNA promoter fragments with this site intact bound p53 in vitro and were transcriptionally activated by wild-type p53 in transient expression assays in SAOS-2 cells. The resident p53-binding site could be functionally substituted by a previously described p53-binding site from the ribosomal gene cluster. A plasmid expressing a mutated version of p53 derived from a patient with Li-Fraumeni syndrome failed to activate the PCNA promoter in the cotransfection assay. In different cell types, activation of the PCNA promoter by the p53-binding sequence correlated with the status of p53. Activation of the PCNA promoter by wild-type p53 depends upon the level of p53 expression. This concentration dependence and cell type specificity reconciles the observations presented here with prior results indicating that wild-type p53 represses the PCNA promoter. These findings provide a mechanism whereby p53 modulates activation of PCNA expression as a cellular response to DNA damage.

MeSH Terms
Base Sequence Cells, Cultured Chloramphenicol O-Acetyltransferase/biosynthesis,genetics DNA Damage Gene Expression Regulation Humans Li-Fraumeni Syndrome/genetics Molecular Sequence Data Mutation Proliferating Cell Nuclear Antigen/biosynthesis,genetics Promoter Regions, Genetic Protein Binding Recombinant Fusion Proteins/biosynthesis Transcription, Genetic Transfection Tumor Suppressor Protein p53/genetics,metabolism
Chemicals
Proliferating Cell Nuclear Antigen Recombinant Fusion Proteins Tumor Suppressor Protein p53 Chloramphenicol O-Acetyltransferase
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Morris G F
Cold Spring Harbor Laboratory, NY 11724, USA.
Bischoff J R
Mathews M B
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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
DOI
10.1073/pnas.93.2.895
Published
1996-01-23
Pages
895-9
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC40154
Subset
IM
Grants
NCI NIH HHS · CA13106 · United States
External Links
PubMed source DOI: 10.1073/pnas.93.2.895 PMC Full Text View journal details
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