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Cited by 81Cancer-related Molecular PathwaysCell death mechanisms and regulationDNA Repair Mechanisms

The biological impact of the human master regulator p53 can be altered by mutations that change the spectrum and expression of its target genes

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Menendez, Daniel, Inga, Alberto, Resnick, Michael A.·2006·Molecular and Cellular Biology
DOI 10.1128/mcb.26.6.2297-2308.2006PMC PMC1430278
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Abstract

Human tumor suppressor p53 is a sequence-specific master regulatory transcription factor that targets response elements (REs) in many genes. p53 missense mutations in the DNA-binding domain are often cancer associated. As shown with systems based on the yeast Saccharomyces cerevisiae, p53 mutants can alter the spectra and intensities of transactivation from individual REs. We address directly in human cells the relationship between changes in the p53 master regulatory network and biological outcomes. Expression of integrated, tightly regulated DNA-binding domain p53 mutants resulted in many patterns of apoptosis and survival following UV or ionizing radiation, or spontaneously. These patterns reflected changes in the spectra and activities of target genes, as demonstrated for P21, MDM2, BAX, and MSH2. Thus, as originally proposed for "master genes of diversity," p53 mutations in human cells can differentially influence target gene transactivation, resulting in a variety of biological consequences which, in turn, might be expected to influence tumor development and therapeutic efficacy.

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  • Many tumor-associated p53 mutants exhibit change-of-spectrum transactivation from various p53 targets.

    “Since many tumor-associated p53 mutants exhibit change-of-spectrum transactivation from various p53 targets, we examined the ability of twenty-five p53 mutants to activate endogenous expression of the TLR gene family in p53 null human cancer cell lines following transfection with p53 mutant expression vectors.”

    From Ligand dependent restoration of human TLR3 signaling and death in p53 mutant cells (2016) · cites this paper as [6]

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Cited by

Sorted by citations

Authors
Menendez, D., Inga, A., & Resnick, M. A.
Affiliations
  • Chromosome Stability Section, Laboratory of Molecular Genetics, National Institute of Environmental Health Sciences, NIH, Research Triangle Park, North Carolina 27709
  • National Institutes of Health (US)
ORCID
Venue
Molecular and Cellular Biology
Publisher
Informa UK Limited
Published
2006-03-01
Volume
26
Issue
6
Pages
2297-2308
ISSN
  • 0270-7306 (ISSN-L)
  • 1098-5549
DOI
10.1128/mcb.26.6.2297-2308.2006
PMC
PMC1430278
OpenAlex
W2129680740
Cited by
81
References
5
Citations by year
2024: 1 · 2023: 7 · 2022: 1 · 2021: 3 · 2020: 1 · 2019: 4 · 2018: 4 · 2016: 7 · 2015: 2 · 2014: 3 · 2013: 5 · 2012: 7
FWCI
5.22
Type
journal article
Language
en
Open access
Licence
journals.asm.org/non-commercial-tdm-license (tdm)
Locations
  • Molecular and Cellular Biology (publishedVersion)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
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 › DNA Repair Mechanisms
Keywords
p53, tumor suppressor, missense mutations, DNA-binding domain, transcription factor target genes, response elements, transcriptional activation, apoptosis, cell survival, ultraviolet radiation, ionizing radiation, p21, MDM2, Bax, MSH2, cancer
MeSH terms
Binding Sites, DNA, Gene Expression Regulation, Humans, Mutation, Promoter Regions, Genetic, Radiation, Ionizing, Transfection, Tumor Cells, Cultured, Ultraviolet Rays, Transcriptional Activation, Tumor Suppressor Protein p53, Apoptosis, Cyclin-Dependent Kinase Inhibitor p21, bcl-2-Associated X Protein, MutS Homolog 2 Protein, Proto-Oncogene Proteins c-mdm2

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