Involvement of RFX1 protein in the regulation of the human proliferating cell nuclear antigen promoter

Liu, M., Lee, B. H., Mathews, M. B. (May 1999) Involvement of RFX1 protein in the regulation of the human proliferating cell nuclear antigen promoter. Journal of Biological Chemistry, 274 (22). pp. 15433-9. ISSN 0021-9258 (Print)

URL: http://www.ncbi.nlm.nih.gov/pubmed/10336433

Abstract

The proliferating cell nuclear antigen (PCNA) is an essential eukaryotic DNA replication factor that is transcriptionally regulated by the adenovirus oncoprotein E1A 243R. Inducibility of the human PCNA promoter by E1A 243R is conferred by the cis-acting PCNA E1A-responsive element (PERE), which associates with the ATF-1, cAMP response element-binding protein (CREB), and RFX1 transcription factors and is modulated by cellular proteins such as the coactivator CREB-binding protein (CBP) and tumor suppressor p107 (Labrie, C., Lee, B. H., and Mathews, M. B. (1995) Nucleic Acids Res. 23, 3732-3741; Lee, B. H., and Mathews, M. B. (1997) Proc. Natl. Acad. Sci. U. S. A. 94, 4481-4486; Lee, B. H., Liu, M., and Mathews, M. B. (1998) J. Virol. 72, 1138-1145). RFX1 also forms a complex with sequences in the PCNA promoter of mouse and rat that share homology with the RFX1 consensus site. To explore the role of RFX1 in regulating the PCNA promoter, we examined the effects of mutations in the human PERE on RFX1 binding and gene expression. Mutations within the RFX1 consensus binding site reduced RFX1 binding, whereas mutations upstream of the site, or on its border, increased RFX1 binding. These mutations also affected the transcriptional activity of PCNA-chloramphenicol acetyltransferase reporter constructs in transient expression assays. The relative transcriptional activity of mutant PCNA promoters, both in the presence and absence of E1A 243R, was inversely related to their ability to complex with RFX1. These findings suggest that the binding of RFX1 is influenced by sequences outside its consensus binding site and that this transcription factor plays an inhibitory role in the regulation of PCNA gene expression.

Item Type: Paper
Uncontrolled Keywords: Adenovirus E1A Proteins/genetics Binding Sites DNA Probes DNA-Binding Proteins/ metabolism Gene Expression Regulation Genes, Reporter Hela Cells Humans Mutation Nuclear Proteins/analysis Proliferating Cell Nuclear Antigen/ genetics Promoter Regions (Genetics) Regulatory Sequences, Nucleic Acid Research Support, U.S. Gov't, P.H.S. Sequence Homology, Nucleic Acid Transcription Factors/ metabolism
Subjects: bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification
organism description > virus > adenovirus
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 > protein structure, function, modification > protein types > transcription factor
CSHL Authors:
Communities: CSHL labs > Herr lab
Depositing User: Kathleen Darby
Date: 28 May 1999
Date Deposited: 28 Apr 2014 16:52
Last Modified: 30 Apr 2014 17:54
Related URLs:
URI: http://repository.cshl.edu/id/eprint/29819

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