Department of Biological Science, Graduate School of Integrated Science and Technology, Shizuoka University, Shizuoka, 422-8529, Japan.
Department of Biological Science, Faculty of Science, Shizuoka University, Shizuoka, 422-8529, Japan.
Biochem Biophys Res Commun. 2018 Dec 2;506(4):932-938. doi: 10.1016/j.bbrc.2018.10.179. Epub 2018 Nov 2.
Cdh1, a substrate-recognition subunit of anaphase-promoting complex/cyclosome (APC/C), is a tumor suppressor, and it is downregulated in various tumor cells in humans. APC/C-Cdh1 is activated from late M phase to G1 phase by antagonizing Cdk1-mediated inhibitory phosphorylation. However, how Cdh1 protein levels are properly regulated is ill-defined. Here we show that Cdh1 is degraded via APC/C-Cdh1 and Skp1-Cullin1-F-box (SCF)-Cdc4 in the budding yeast Saccharomyces cerevisiae. Cdh1 degradation was promoted by forced localization of Cdh1 into the nucleus, where APC/C and SCF are present. Cdk1 promoted APC/C-Cdh1-mediated Cdh1 degradation, whereas polo kinase Cdc5 elicited SCF-Cdc4-mediated degradation. Thus, Cdh1 degradation is controlled via multiple pathways.
Cdh1 是后期促进复合物/细胞周期蛋白(APC/C)的底物识别亚基,是一种肿瘤抑制因子,在人类的各种肿瘤细胞中均下调。APC/C-Cdh1 通过拮抗 Cdk1 介导的抑制性磷酸化,从晚期 M 期到 G1 期被激活。然而,Cdh1 蛋白水平是如何被正确调节的尚不清楚。在这里,我们表明 Cdh1 在 budding 酵母 Saccharomyces cerevisiae 中通过 APC/C-Cdh1 和 Skp1-Cullin1-F-box (SCF)-Cdc4 进行降解。Cdh1 的降解是通过强迫将 Cdh1 定位到核内来促进的,APC/C 和 SCF 都存在于核内。Cdk1 促进了 APC/C-Cdh1 介导的 Cdh1 降解,而 Polo 激酶 Cdc5 则引发了 SCF-Cdc4 介导的降解。因此,Cdh1 的降解是通过多种途径控制的。