Regulation of the human proliferating cell nuclear antigen promoter by the adenovirus E1A-associated protein p107

Lee, B. H., Liu, M., Mathews, M. B. (February 1998) Regulation of the human proliferating cell nuclear antigen promoter by the adenovirus E1A-associated protein p107. Journal of Virology, 72 (2). pp. 1138-45. ISSN 0022-538X

URL: http://www.ncbi.nlm.nih.gov/pubmed/9445010

Abstract

The adenovirus E1A 243R oncoprotein is capable of transactivating the expression of the human proliferating cell nuclear antigen (PCNA) promoter. Mutational analysis of the E1A 243R protein suggested that both its p300/CBP- and p107-binding regions are required for optimal induction of the PCNA promoter (C. Kannabiran, G. F. Morris, C. Labrie, and M. B. Mathews, J. Virol. 67:425-437, 1993). We show that overexpression of p107 antagonizes the induction of PCNA by E1A 243R in transient expression assays. This inhibition is largely independent of p107's ability to interact with E1A 243R, because p107 mutants unable to bind to E1A 243R retain the ability to repress the E1A-activated PCNA promoter. Electrophoretic mobility shift assays with the PCNA promoter detected the presence of p107 in one of the major DNA-protein complexes, EH1, formed with HeLa cell nuclear extracts. Promoter mutations that disrupt the formation of complex EH1 abrogated p107's ability to reverse E1A 243R-induced PCNA expression. The same mutations characterize a sequence important for the binding of transcription factor RFX1 (C. Labrie, G. F. Morris, and M. B. Mathews, Nucleic Acids Res. 23:3732-3741, 1995), implying that p107 antagonizes E1A 243R-induced PCNA expression through this RFX1-binding site. Our data are suggestive of a novel cooperative mechanism for transactivation of PCNA expression, in which E1A 243R relieves transcriptional repression exerted by p107 on the promoter.

Item Type: Paper
Uncontrolled Keywords: Adenoviridae/ genetics DNA Mutational Analysis Gene Expression Regulation Hela Cells Humans Nuclear Proteins/ genetics Proliferating Cell Nuclear Antigen/ genetics Promoter Regions (Genetics)/ genetics Research Support, U.S. Gov't, P.H.S. Retinoblastoma-Like Protein p107
Subjects: bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types > E1A protein
organism description > virus > adenovirus
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > genes, structure and function > gene expression
diseases & disorders > cancer > cancer types > retinoblastoma
CSHL Authors:
Communities: CSHL labs > Herr lab
Depositing User: Kathleen Darby
Date: February 1998
Date Deposited: 01 May 2014 19:18
Last Modified: 08 May 2014 19:08
PMCID: PMC124588
Related URLs:
URI: http://repository.cshl.edu/id/eprint/29905

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