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Distinct promoter elements mediate the co-operative effect of Brn-3a and p53 on the p21 promoter and their antagonism on the Bax promoter

Perez-Sanchez, C; Budhram-Mahadeo, VS; Latchman, DS; (2002) Distinct promoter elements mediate the co-operative effect of Brn-3a and p53 on the p21 promoter and their antagonism on the Bax promoter. Nucleic Acids Res , 30 (22) 4872 - 4880. 10.1093/nar/gkf610. Green open access

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Abstract

Although the promoters of both the Bax and p21 genes are activated by p53, they differ in the effect on this activation of the POU family transcription factor Brn-3a. Thus, Brn-3a inhibits activation of the Bax promoter by p53 but enhances the ability of p53 to activate the p21 promoter. We demonstrate that repression of p53-mediated activation of the Bax promoter involves a complex upstream sequence in which two Brn-3a response elements flank the p53 response element. In contrast, a minimal p21 promoter is activated by Brn-3a and such activation cannot be abolished without abolishing basal promoter activity. Moreover, synergistic activation by Brn-3a and p53 continues to be observed when the p53-binding sites in the p21 promoter are substituted by the Bax p53 site or by the region of the Bax promoter essential for Brn-3a-mediated repression, indicating that the p21 core promoter plays a central role in this response. The significance of these effects is discussed in terms of the different responses of the Bax and p21 promoters and the overlapping but distinct roles of Brn-3a and p53 in neuronal growth arrest and apoptosis.

Type: Article
Title: Distinct promoter elements mediate the co-operative effect of Brn-3a and p53 on the p21 promoter and their antagonism on the Bax promoter
Location: England
Open access status: An open access version is available from UCL Discovery
DOI: 10.1093/nar/gkf610
Publisher version: http://dx.doi.org/ 10.1093/nar/gkf610
Language: English
Additional information: PMCID: PMC137158. This article was original published in Nucleic Acids Research by Oxford University Press, 2002
Keywords: Animals, Base Sequence, Binding Sites, Cell Line, Cyclin-Dependent Kinase Inhibitor p21, Cyclins, DNA-Binding Proteins, Luciferases, Molecular Sequence Data, Mutation, Neurons, Promoter Regions, Genetic, Proto-Oncogene Proteins, Proto-Oncogene Proteins c-bcl-2, Response Elements, Transcription Factor Brn-3, Transcription Factors, Transcriptional Activation, Tumor Suppressor Protein p53, bcl-2-Associated X Protein
UCL classification: UCL
UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Cardiovascular Science
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Cardiovascular Science > Pre-clinical and Fundamental Science
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health > ICH - Directors Office
URI: https://discovery.ucl.ac.uk/id/eprint/29058
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