Cyclin G Recruits PP2A to Dephosphorylate Mdm2
Open accessAbstract
The function of cyclin G, a commonly induced p53 target, has remained elusive. We show that cyclin G forms a quaternary complex in vivo and in vitro with enzymatically active phosphatase 2A (PP2A) holoenzymes containing B' subunits. Interestingly, cyclin G also binds in vivo and in vitro to Mdm2 and markedly stimulates the ability of PP2A to dephosphorylate Mdm2 at T216. Consistent with these data, cyclin G null cells have both Mdm2 that is hyperphosphorylated at T216 and markedly higher levels of p53 protein when compared to wild-type cells. Cyclin G expression also results in reduced phosphorylation of human Hdm2 at S166. Thus, our data suggest that cyclin G recruits PP2A in order to modulate the phosphorylation of Mdm2 and thereby to regulate both Mdm2 and p53.
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MDM2 function is supported through cyclin G1, which activates MDM2 through dephosphorylation, and CCNG1 is a p53 target itself.
“MDM2 function is supported through cyclin G1, which activates MDM2 through dephosphorylation218 and CCNG1 is a p53 target itself.219”
From Census and evaluation of p53 target genes (2017) · cites this paper as [218]
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- Authors
- Okamoto, K., Li, H., Jensen, M. R., Zhang, T., Taya, Y., Thorgeirsson, S. S., & Prives, C.
- Affiliations
- National Cancer Center Research Institute (JP)
- Columbia University (US)
- National Institutes of Health (US)
- Corresponding author
- Prives, Carol
- Venue
- Molecular Cell
- Publisher
- Elsevier BV
- Published
- 2002-04
- Volume
- 9
- Issue
- 4
- Pages
- 761-771
- ISSN
- 1097-2765 (ISSN-L)
- OpenAlex
- W2169756921
- Cited by
- 215
- References
- 77
- Citations by year
- 2026: 4 · 2025: 5 · 2023: 8 · 2022: 2 · 2021: 4 · 2020: 4 · 2019: 5 · 2018: 5 · 2017: 7 · 2016: 12 · 2015: 11 · 2014: 6 · 2013: 10 · 2012: 12
- FWCI
- 7.12
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Molecular Cell (publishedVersion)
- PubMed (publishedVersion)
- Institutional Repositories DataBase (IRDB) (submittedVersion)
- Funders
- National Cancer Institute (CA 58316)
- Topics
- Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › PI3K/AKT/mTOR signaling in cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Tyrosine Phosphatases
- Keywords
- cyclin G, protein phosphatase 2A, MDM2, p53, protein dephosphorylation, quaternary complex, p53 regulation, p53 target genes
- MeSH terms
- Animals, Antifungal Agents, Catalysis, Chlorocebus aethiops, Enzyme Inhibitors, Humans, Nuclear Proteins, Phosphoprotein Phosphatases, Phosphorylation, Protein Binding, Protein Processing, Post-Translational, Proto-Oncogene Proteins, Pyrans, Recombinant Fusion Proteins, Species Specificity, Spiro Compounds, Transfection, Tumor Suppressor Protein p53, Cyclins, Cyclosporine, Phosphotyrosine, Okadaic Acid, COS Cells, Protein Subunits, Protein Interaction Mapping, Macromolecular Substances, Mice, Proto-Oncogene Proteins c-mdm2, Protein Phosphatase 2, Cyclin G, Cyclin G1
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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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