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Cyclin D1-cdk4 induce runx2 ubiquitination and degradation.

Runx2 is a Runt domain transcription factor involved in the activation of genes encoding osteoblast and chondrocyte-specific proteins. Runx2 activity is regulated by transcriptional and post-transcriptional mechanisms. The functional significance of the post-translational modification of Runx2 has not been fully defined. We show that cyclin D1-Cdk4 induce Runx2 degradation in an ubiquitination-proteasome-dependent manner. Mutagenesis of Runx2 serine-472, a consensus Cdk site, to alanine increases the half-life of Runx2 and causes loss of sensitivity to cyclin D1-induced Runx2 degradation. The targeted Runx2 degradation by cyclin D1 identifies a novel mechanism through which Runx2 activity is regulated coordinately with the cell cycle machinery in bone cells.

Pubmed ID: 16613857 RIS Download

Mesh terms: Animals | COS Cells | Cell Cycle | Cercopithecus aethiops | Core Binding Factor Alpha 1 Subunit | Cyclin D1 | Cyclin-Dependent Kinase 4 | Mice | Mice, Inbred C3H | Mutagenesis, Site-Directed | Proteasome Endopeptidase Complex | Protein Binding | Serine | Ubiquitin

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Associated grants

  • Agency: NIAMS NIH HHS, Id: AR 38945
  • Agency: NIAMS NIH HHS, Id: R01 AR051189-03
  • Agency: NIAMS NIH HHS, Id: R01 AR054465-01
  • Agency: NIAMS NIH HHS, Id: R01 AR038945
  • Agency: NIAMS NIH HHS, Id: R01 AR051189
  • Agency: NIAMS NIH HHS, Id: R01 AR051189-04
  • Agency: NIAMS NIH HHS, Id: R01 AR054465
  • Agency: NIAMS NIH HHS, Id: AR 048920
  • Agency: NIAMS NIH HHS, Id: K02 AR052411-01A2
  • Agency: NIAMS NIH HHS, Id: K02 AR052411
  • Agency: NIAMS NIH HHS, Id: R03 AR048920
  • Agency: NIAMS NIH HHS, Id: AR 051189

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