Induction of PPM1D following DNA-damaging treatments through a conserved p53 response element coincides with a shift in the use of transcription initiation sites
Open accessAbstract
PPM1D (Wip1), a type PP2C phosphatase, is expressed at low levels in most normal tissues but is overexpressed in several types of cancers. In cells containing wild-type p53, the levels of PPM1D mRNA and protein increase following exposure to genotoxic stress, but the mechanism of regulation by p53 was unknown. PPM1D also has been identified as a CREB-regulated gene due to the presence of a cyclic AMP response element (CRE) in the promoter. Transient transfection and chromatin immunoprecipitation experiments in HCT116 cells were used to characterize a conserved p53 response element located in the 5' untranslated region (UTR) of the PPM1D gene that is required for the p53-dependent induction of transcription from the human PPM1D promoter. CREB binding to the CRE contributes to the regulation of basal expression of PPM1D and directs transcription initiation at upstream sites. Following exposure to ultraviolet (UV) or ionizing radiation, the abundance of transcripts with short 5' UTRs increased in cells containing wild-type p53, indicating increased utilization of downstream transcription initiation sites. In cells containing wild-type p53, exposure to UV resulted in increased PPM1D protein levels even when PPM1D mRNA levels remained constant, indicating post-transcriptional regulation of PPM1D protein levels.
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PPM1D (WIP1) is also a p53 target and encodes for a phosphatase that confers a negative feedback loop through p53 dephosphorylation and cell cycle checkpoint abrogation.
“PPM1D (WIP1) is also a p53 target and encodes for a phosphatase that confers a negative feedback loop through p53 dephosphorylation and cell cycle checkpoint abrogation.40, 220, 221”
From Census and evaluation of p53 target genes (2017) · cites this paper as [40]
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Self-citation
- Authors
- Rossi, M., Demidov, O. N., Anderson, C. W., Appella, E., & Mazur, S. J.
- Affiliations
- National Institutes of Health (US)
- Corresponding author
- Mazur, Sharlyn J.
- Venue
- Nucleic Acids Research
- Publisher
- Oxford University Press (OUP)
- Published
- 2008-11-10
- Volume
- 36
- Issue
- 22
- Pages
- 7168-7180
- ISSN
- 0305-1048 (ISSN-L)
- 1362-4962
- PMC
- PMC2602757
- OpenAlex
- W2113628074
- Cited by
- 57
- References
- 83
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 2 · 2021: 4 · 2020: 3 · 2019: 1 · 2018: 1 · 2017: 2 · 2016: 4 · 2015: 3 · 2014: 7 · 2013: 4 · 2012: 6
- FWCI
- 2.99
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Nucleic Acids Research (publishedVersion, cc-by-nc)
- PubMed Central (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- Funders
- U.S. Department of Energy
- National Institutes of Health
- National Cancer Institute
- Biological and Environmental Research
- Brookhaven National Laboratory
- Topics
- Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Tyrosine Phosphatases
- Keywords
- PPM1D, Wip1, p53 response elements, 5' untranslated region, transcription start sites, CREB, cyclic AMP response element, PP2C protein phosphatase, DNA damage response, ultraviolet radiation, ionizing radiation, post-transcriptional regulation, HCT116 cells
- MeSH terms
- Protein Phosphatase 2C, Animals, Base Sequence, Chromatin, DNA Damage, Gene Expression Regulation, Humans, Phosphoprotein Phosphatases, Phylogeny, Promoter Regions, Genetic, Radiation, Ionizing, RNA, Messenger, Ultraviolet Rays, Tumor Suppressor Protein p53, Conserved Sequence, Cyclic AMP Response Element-Binding Protein, 5' Untranslated Regions, Response Elements, Transcription Initiation Site, Cell Line, Tumor, Mice
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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