Zhou P, Howley P M
Department of Pathology, Harvard Medical School, Boston, MA 02115, USA.
Mol Cell. 1998 Nov;2(5):571-80. doi: 10.1016/s1097-2765(00)80156-2.
The S. cerevisiae SCFCdc4p ubiquitin-protein ligase complex promotes cell cycle transitions through degradation of cell cycle regulators. To investigate SCFCdc4p regulation in vivo, we examined the stability of individual SCFCdc4p components. Whereas Cdc53p and Skp1p were stable, Cdc4p, the F box-containing component responsible for substrate recognition, was short lived and subject to SCF-mediated ubiquitination. Grr1p, another F box component of SCF complexes, was also ubiquitinated. A stable truncated Cdc4pF-beta-gal hybrid protein capable of binding Skp1p and entering into an SCF complex interfered with proteolysis of SCF targets and inhibited cell proliferation. The finding that the F box-containing SCF components are unstable suggests a mechanism of regulating SCF function through ubiquitination and proteolysis of F box components.
酿酒酵母SCFCdc4p泛素 - 蛋白连接酶复合物通过降解细胞周期调节因子促进细胞周期转换。为了在体内研究SCFCdc4p的调控机制，我们检测了SCFCdc4p各个组分的稳定性。Cdc53p和Skp1p是稳定的，而负责底物识别的含F盒组分Cdc4p寿命较短，并受到SCF介导的泛素化作用。Grr1p是SCF复合物的另一个F盒组分，也会发生泛素化。一种能够结合Skp1p并进入SCF复合物的稳定截短型Cdc4pF-β-半乳糖杂合蛋白干扰了SCF靶标的蛋白水解并抑制细胞增殖。含F盒的SCF组分不稳定这一发现提示了一种通过F盒组分的泛素化和蛋白水解来调节SCF功能的机制。
