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

Morris, G. F., Bischoff, J. R., Mathews, M. B. (January 1996) Transcriptional activation of the human proliferating-cell nuclear antigen promoter by p53. Proceedings of the National Academy of Sciences, 93 (2). pp. 895-9. ISSN 0027-8424 (Print)

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URL: http://www.ncbi.nlm.nih.gov/pubmed/8570655

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.

Item Type: Paper
Uncontrolled Keywords: 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 (Genetics) Protein Binding Recombinant Fusion Proteins/biosynthesis Research Support, U.S. Gov't, P.H.S. Transcription, Genetic Transfection Tumor Suppressor Protein p53/genetics/ metabolism
Subjects: bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > transcription
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > genes, structure and function > gene expression
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > genes, structure and function > genes: types > p53
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types
Investigative techniques and equipment > transfection
CSHL Authors:
Communities: CSHL labs > Beach lab
Depositing User: Kathleen Darby
Date: 23 January 1996
Date Deposited: 13 May 2014 17:28
Last Modified: 13 Sep 2019 16:38
PMCID: PMC40154
Related URLs:
URI: http://repository.cshl.edu/id/eprint/30093

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