Cited by 144Cancer-related Molecular PathwaysCell death mechanisms and regulationGenomics and Chromatin Dynamics

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p53 Suppresses the Activation of the Bcl-2 Promoter by the Brn-3a POU Family Transcription Factor

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Budhram-Mahadeo, Vishwanie, Morris, Peter J., Smith, Martin D., Midgley, Carol A., Boxer, Linda M., Latchman, David S.·1999·Journal of Biological Chemistry

DOI 10.1074/jbc.274.21.15237

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Abstract

The Brn-3a POU family transcription factor has been shown to strongly activate expression of the Bcl-2 proto-oncogene and thereby protect neuronal cells from programmed cell death (apoptosis). This activation of the Bcl-2 promoter by Brn-3a is strongly inhibited by the p53 anti-oncogene protein. This inhibitory effect of p53 on Brn-3a-mediated transactivation is observed with nonoverlapping gene fragments containing either the Bcl-2 p1 or p2 promoters but is not observed with other Brn-3a-activated promoters such as in the gene encoding alpha-internexin or with an isolated Brn-3a binding site from the Bcl-2 promoter linked to a heterologous promoter. In contrast, p53 mutants, which are incapable of binding to DNA, do not affect Brn-3a-mediated activation of the Bcl-2 p1 and p2 promoters. Moreover, Brn-3a and p53 have been shown to bind to adjacent sites in the p2 promoter and to directly interact with one another, both in vitro and in vivo, with this interaction being mediated by the POU domain of Brn-3a and the DNA binding domain of p53. The significance of these effects is discussed in terms of the antagonistic effects of Bcl-2 and p53 on the rate of apoptosis and the overexpression of Brn-3a in specific tumor cell types.

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Authors: Budhram-Mahadeo, V., Morris, P. J., Smith, M. D., Midgley, C. A., Boxer, L. M., & Latchman, D. S.
Affiliations: University College London (GB)
University of Dundee (GB)
Stanford Medicine (US)
Corresponding author: Latchman, David S.
ORCID: Budhram-Mahadeo, Vishwanie
Venue: Journal of Biological Chemistry
Publisher: Elsevier BV
Published: 1999-05
Volume: 274
Issue: 21
Pages: 15237-15244
ISSN: 0021-9258 (ISSN-L)
DOI: 10.1074/jbc.274.21.15237
OpenAlex: W2131045322
Cited by: 144
References: 40
Citations by year: 2026: 2 · 2025: 2 · 2024: 2 · 2023: 3 · 2022: 1 · 2021: 4 · 2020: 4 · 2019: 3 · 2018: 6 · 2017: 5 · 2016: 2 · 2015: 2 · 2014: 6 · 2013: 10 · 2012: 2
FWCI: 3.55
Type: journal article
Language: en
Open access: hybrid
doi.org
Licence: cc-by
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
creativecommons.org/licenses/by/4.0/ (vor, 7831 d)
Locations: Journal of Biological Chemistry (publishedVersion, cc-by)
PubMed (publishedVersion)
UCL Discovery (University College London) (submittedVersion)
Topics: Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
Keywords: p53, Brn3a, POU transcription factors, Bcl-2, Bcl-2 promoter, transcriptional repression, protein-protein interaction, POU domain, DNA-binding domain, apoptosis, neuronal survival, alpha-internexin
MeSH terms: Cells, Cultured, DNA-Binding Proteins, Promoter Regions, Genetic, Transcription Factors, Genes, p53, Genes, bcl-2, Transcription Factor Brn-3

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p53 Suppresses the Activation of the Bcl-2 Promoter by the Brn-3a POU Family Transcription Factor

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