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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

Authors

  • Shen R
  • Wang X
  • Drissi H
  • Liu F
  • O'Keefe RJ
  • Chen D

Journal

The Journal of biological chemistry

Publication Data

June 16, 2006

Associated Grants

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

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