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.
Shen
Run
R
Department of Orthopaedics, Center for Musculoskeletal Research, University of Rochester School of Medicine, Rochester, NY 14642, USA.
Wang
Xiumei
X
Drissi
Hicham
H
Liu
Fang
F
O'Keefe
Regis J
RJ
Chen
Di
D
D000818:Animals; D019556:COS Cells; D002453:Cell Cycle; D002522:Chlorocebus aethiops; D050659:Core Binding Factor Alpha 1 Subunit / Q000502:physiology*; D019938:Cyclin D1 / Q000378:metabolism / Q000502:physiology*; D051358:Cyclin-Dependent Kinase 4 / Q000502:physiology*; D051379:Mice; D008809:Mice, Inbred C3H; D016297:Mutagenesis, Site-Directed; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D011485:Protein Binding; D012694:Serine / Q000737:chemistry; D025801:Ubiquitin / Q000737:chemistry*
D050659:Core Binding Factor Alpha 1 Subunit; D025801:Ubiquitin; D019938:Cyclin D1; D012694:Serine; D051358:Cyclin-Dependent Kinase 4; D046988:Proteasome Endopeptidase Complex