Dinarina Ana, Santamaria Patricia G, Nebreda Angel R
CNIO (Spanish National Cancer Center), Madrid, Spain.
FEBS Lett. 2009 Sep 3;583(17):2772-8. doi: 10.1016/j.febslet.2009.07.028. Epub 2009 Jul 19.
Cell cycle progression is regulated by cyclin-dependent kinases (CDKs), whose activation requires the binding of regulatory subunits named cyclins. RINGO/Speedy A is a mammalian protein that has no amino acid sequence homology with cyclins but can activate CDKs. Here we show that RINGO/Speedy A is a highly unstable protein whose expression and phosphorylation are periodically regulated during the cell cycle. RINGO/Speedy A is degraded by the proteasome and the process involves the ubiquitin ligase SCF(Skp2). Overexpression of a stabilized RINGO/Speedy A form results in the accumulation of high levels of RINGO/Speedy A at late stages of mitosis, which interfere with cytokinesis and chromosome decondensation. Our data show that tight regulation of RINGO/Speedy A is important for the somatic cell cycle.
细胞周期进程受细胞周期蛋白依赖性激酶（CDK）调控，其激活需要名为细胞周期蛋白的调节亚基结合。RINGO/Speedy A是一种与细胞周期蛋白没有氨基酸序列同源性但能激活CDK的哺乳动物蛋白。我们在此表明，RINGO/Speedy A是一种高度不稳定的蛋白，其表达和磷酸化在细胞周期中受到周期性调控。RINGO/Speedy A被蛋白酶体降解，该过程涉及泛素连接酶SCF（Skp2）。稳定形式的RINGO/Speedy A过表达导致在有丝分裂后期积累高水平的RINGO/Speedy A，这会干扰胞质分裂和染色体解聚。我们的数据表明，对RINGO/Speedy A的严格调控对体细胞周期很重要。
