Cited by 215Cancer-related Molecular PathwaysPI3K/AKT/mTOR signaling in cancerProtein Tyrosine Phosphatases

Cyclin G Recruits PP2A to Dephosphorylate Mdm2

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Okamoto, Koji, Li, Hongyun, Jensen, Michael R, Zhang, Tingting, Taya, Yoichi, Thorgeirsson, Snorri S, Prives, Carol·2002·Molecular Cell

Abstract

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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Crossref · 10.1016/s1097-2765(02)00504-x

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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
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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