Shen Run, Wang Xiumei, Drissi Hicham, Liu Fang, O'Keefe Regis J, Chen Di
Department of Orthopaedics, Center for Musculoskeletal Research, University of Rochester School of Medicine, Rochester, NY 14642, USA.
J Biol Chem. 2006 Jun 16;281(24):16347-53. doi: 10.1074/jbc.M603439200. Epub 2006 Apr 13.
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.
Runx2是一种Runt结构域转录因子，参与编码成骨细胞和软骨细胞特异性蛋白的基因的激活。Runx2的活性受转录和转录后机制调控。Runx2翻译后修饰的功能意义尚未完全明确。我们发现细胞周期蛋白D1-Cdk4以泛素化-蛋白酶体依赖的方式诱导Runx2降解。将Runx2丝氨酸-472（一个共有Cdk位点）突变为丙氨酸可增加Runx2的半衰期，并导致对细胞周期蛋白D1诱导的Runx2降解的敏感性丧失。细胞周期蛋白D1对Runx2的靶向降解确定了一种新机制，通过该机制Runx2的活性与骨细胞中的细胞周期机制协同调节。
