p53 Stimulates Transcription from the Human Transforming Growth Factor α Promoter: a Potential Growth-Stimulatory Role for p53

Shin, Tae Ho; Paterson, Andrew J.; Kudlow, Jeffrey E.

doi:10.1128/mcb.15.9.4694

Cited by 78Cancer-related Molecular PathwaysTGF-β signaling in diseasesGenomics and Chromatin Dynamics

p53 Stimulates Transcription from the Human Transforming Growth Factor α Promoter: a Potential Growth-Stimulatory Role for p53

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Shin, Tae Ho, Paterson, Andrew J., Kudlow, Jeffrey E.·1995·Molecular and Cellular Biology

DOI 10.1128/mcb.15.9.4694PMC PMC230712

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Abstract

Physical and chemical agents can damage the genome. Part of the protective response to this damage is the increased expression of p53. p53, a transcription factor, controls the expression of genes, leading to cell cycle arrest and apoptosis. Another protective mechanism is the proliferative response required to replace the damaged cells. This proliferation is likely to be signaled by growth factors. In this communication, we show that the transforming growth factor alpha (TGF-alpha) gene is a direct target for p53-mediated transcriptional activation. In a stable cell line containing an inducible p53 construct, p53 induction leads to a threefold accumulation of the native TGF-alpha mRNA. IN cotransfection assays using a TGF-alpha promoter reporter construct, we show that expression of wild-type but not mutant p53 increases transcriptional activity of the TGF-alpha promoter by approximately 2.5-fold. In vitro, wild-type p53 binds to a consensus binding site found in the proximal portion of the promoter, and this sequence is necessary for the p53 transcriptional response. Furthermore, this element confers p53 induction to the otherwise nonresponsive adenovirus major late promoter. In addition to these results, we found that the TGF-alpha promoter contains a nonconsensus but functional TATA box-binding protein-binding site approximately 30 bp upstream of the transcription start site. Although p53 can repress transcription from promoters containing a TATA box, the nonconsensus TGF-alpha TATA motif is resistant to this effect. On the basis of these results, we propose that p53 may play a dual role, which includes both the elimination of irreparably genetically damage cells and the proliferative response necessary for their replacement, in the response to physical-chemical damage.

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Authors: Shin, T. H., Paterson, A. J., & Kudlow, J. E.
Affiliations: University of Alabama at Birmingham (US)
ORCID: Paterson, Andrew J.
Venue: Molecular and Cellular Biology
Publisher: Informa UK Limited
Published: 1995-09-01
Volume: 15
Issue: 9
Pages: 4694-4701
ISSN: 0270-7306 (ISSN-L)
1098-5549
DOI: 10.1128/mcb.15.9.4694
PMC: PMC230712
OpenAlex: W1790840575
Cited by: 78
References: 48
Citations by year: 2026: 1 · 2022: 2 · 2018: 1 · 2017: 1 · 2016: 1 · 2015: 1 · 2014: 2 · 2013: 2 · 2012: 1
FWCI: 3.43
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Licence: journals.asm.org/non-commercial-tdm-license (tdm)
Locations: Molecular and Cellular Biology (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Funders: National Institutes of Health
National Institute of Diabetes and Digestive and Kidney Diseases (R01DK043652, DK-43652)
Topics: Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › TGF-β signaling in diseases
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
Keywords: p53, transforming growth factor-alpha, transcriptional activation, p53 binding sites, TATA-binding protein, TATA box, adenovirus major late promoter, cell proliferation, DNA damage response, growth promotion, mutant p53
MeSH terms: Adenoviridae, Base Sequence, Cell Line, DNA Damage, DNA Mutational Analysis, Fluorescent Antibody Technique, Gene Expression Regulation, Glioma, Humans, Molecular Sequence Data, Precipitin Tests, Promoter Regions, Genetic, Protein Binding, Transcription, Genetic, Transfection, Viral Proteins, Blotting, Northern, Blotting, Western, Tumor Suppressor Protein p53, Transforming Growth Factor alpha, TATA Box, Sequence Deletion

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p53 Stimulates Transcription from the Human Transforming Growth Factor α Promoter: a Potential Growth-Stimulatory Role for p53

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