Cyclin D1-Cdk4 induce Runx2 ubiquitination and degradation

Run Shen, Xiumei Wang, Hicham Drissi, Fang Liu, Regis J. O'Keefe, Di Chen

Research output: Contribution to journalArticlepeer-review

100 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)16347-16353
Number of pages7
JournalJournal of Biological Chemistry
Volume281
Issue number24
DOIs
StatePublished - Jun 16 2006

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