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FRTL-5細胞の増殖とくにG1/S期移行に不可欠なメバロン酸代謝産物の同定とその分子機構 : geranylgeranylpyrophosphateによる癌抑制遺伝子p27の分解促進とCdk2活性化作用

  • P27
  • Cdk2
  • Mevalonate
  • Geranylgeranylpyrophosphate
  • Cell Cycle
  • Ndc:490
  • Biology


Cyclin-dependent kinase (Cdk) enzymes are activated for entry into the S phase of the cell cycle. In growth-stimulated rat thyroid FRTL-5 cells, the elimination of Cdk inhibitor protein, p27^<Kip1>, and the activation of Cdk2 during the G1/S transition is required for the cell cycle progression. Pravastatin, an inhibitor of 3-hydroxy-3-methylglutaryl-CoA reductase, prevents the elimination of p27 and leads to G1 arrest. Mevalonate and its metabolite, geranylIgeranylpyrophosphate, but not farnesyl pyrophosphate, allow Cdk2 activation by causing the elimination of p27 through the acceleration of its degradation. These results indicate that among mevalonate metabolites, geranylgeranylpyrophosphate is absolutely required for the elimination of p27 followed by Cdk2 activation, and promote the degradation of p27 during G1/S transition in growth-stimulated FRTL-5 cells.

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