Cited by 57Cancer-related Molecular PathwaysGenomics and Chromatin DynamicsProtein Tyrosine Phosphatases

Induction of PPM1D following DNA-damaging treatments through a conserved p53 response element coincides with a shift in the use of transcription initiation sites

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Rossi, Matteo, Demidov, Oleg N., Anderson, Carl W., Appella, Ettore, Mazur, Sharlyn J.·2008·Nucleic Acids Research

Abstract

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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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
Published
2008-11-10
Volume
36
Issue
22
Pages
7168-7180
ISSN
  • 0305-1048 (ISSN-L)
  • 1362-4962
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
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

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