Cyclin G Recruits PP2A to Dephosphorylate Mdm2

Mol Cell. 2002 Apr;9(4):761-71. doi: 10.1016/s1097-2765(02)00504-x.

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Antifungal Agents / pharmacology
  • COS Cells
  • Catalysis
  • Chlorocebus aethiops
  • Cyclin G
  • Cyclin G1
  • Cyclins / chemistry
  • Cyclins / physiology*
  • Cyclosporine / pharmacology
  • Enzyme Inhibitors / pharmacology
  • Humans
  • Macromolecular Substances
  • Mice
  • Nuclear Proteins*
  • Okadaic Acid / pharmacology
  • Phosphoprotein Phosphatases / antagonists & inhibitors
  • Phosphoprotein Phosphatases / chemistry
  • Phosphoprotein Phosphatases / metabolism*
  • Phosphorylation
  • Phosphotyrosine / metabolism
  • Protein Binding
  • Protein Interaction Mapping
  • Protein Phosphatase 2
  • Protein Processing, Post-Translational / physiology*
  • Protein Subunits
  • Proto-Oncogene Proteins / metabolism*
  • Proto-Oncogene Proteins c-mdm2
  • Pyrans*
  • Recombinant Fusion Proteins / metabolism
  • Species Specificity
  • Spiro Compounds*
  • Transfection
  • Tumor Suppressor Protein p53 / metabolism*

Substances

  • Antifungal Agents
  • CCNG1 protein, human
  • Ccng1 protein, mouse
  • Cyclin G
  • Cyclin G1
  • Cyclins
  • Enzyme Inhibitors
  • Macromolecular Substances
  • Nuclear Proteins
  • Protein Subunits
  • Proto-Oncogene Proteins
  • Pyrans
  • Recombinant Fusion Proteins
  • Spiro Compounds
  • Tumor Suppressor Protein p53
  • tautomycin
  • Okadaic Acid
  • Phosphotyrosine
  • Cyclosporine
  • MDM2 protein, human
  • Mdm2 protein, mouse
  • Proto-Oncogene Proteins c-mdm2
  • Phosphoprotein Phosphatases
  • Protein Phosphatase 2