Cyclin G recruits PP2A to dephosphorylate Mdm2.
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.
Mesh Terms:
Animals, Antifungal Agents, COS Cells, Catalysis, Cercopithecus aethiops, Cyclin G, Cyclin G1, Cyclins, Cyclosporine, Enzyme Inhibitors, Humans, Macromolecular Substances, Mice, Nuclear Proteins, Okadaic Acid, Phosphoprotein Phosphatases, Phosphorylation, Phosphotyrosine, Protein Binding, Protein Interaction Mapping, Protein Phosphatase 2, Protein Processing, Post-Translational, Protein Subunits, Proto-Oncogene Proteins, Proto-Oncogene Proteins c-mdm2, Pyrans, Recombinant Fusion Proteins, Species Specificity, Spiro Compounds, Transfection, Tumor Suppressor Protein p53
Animals, Antifungal Agents, COS Cells, Catalysis, Cercopithecus aethiops, Cyclin G, Cyclin G1, Cyclins, Cyclosporine, Enzyme Inhibitors, Humans, Macromolecular Substances, Mice, Nuclear Proteins, Okadaic Acid, Phosphoprotein Phosphatases, Phosphorylation, Phosphotyrosine, Protein Binding, Protein Interaction Mapping, Protein Phosphatase 2, Protein Processing, Post-Translational, Protein Subunits, Proto-Oncogene Proteins, Proto-Oncogene Proteins c-mdm2, Pyrans, Recombinant Fusion Proteins, Species Specificity, Spiro Compounds, Transfection, Tumor Suppressor Protein p53
Mol. Cell
Date: Apr. 01, 2002
PubMed ID: 11983168
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