Lim H H, Goh P Y, Surana U
Institute of Molecular and Cell Biology, Singapore.
Curr Biol. 1998 Feb 12;8(4):231-4. doi: 10.1016/s0960-9822(98)70088-0.
Chromosome separation during the cell-cycle transition from metaphase to anaphase requires the proteolytic destruction of anaphase inhibitors such as Pds1 [1-3]. Proteolysis of Pds1 is mediated by a ubiquitin-protein ligase, the anaphase-promoting complex (APC) or cyclosome [4,5]. The APC is also necessary for the ubiquitin-dependent degradation of mitotic cyclins in late telophase as cells exit mitosis [6-9]. Although phosphorylation seems to be involved [10], it is not clear what activates the APC at the onset of anaphase. In Saccharomyces cerevisiae, chromosome segregation also requires the CDC20 gene, whose product contains WD40 repeats [11,12]. We have investigated the functional relationship between the APC and the Cdc20 protein. We present evidence that strongly suggests that Cdc20 is an essential regulator of APC-dependent proteolysis such that in the absence of Cdc20, cells are unable to degrade either Pds1 at the onset of anaphase or the mitotic cyclin Clb2 during telophase. This notion is consistent with our observations that Cdc20 is localized in the nucleus and co-immunoprecipitates with an APC component, Cdc23.
在细胞周期从中期到后期的转变过程中，染色体分离需要对后期抑制因子（如Pds1）进行蛋白水解破坏[1-3]。Pds1的蛋白水解由泛素-蛋白连接酶后期促进复合物（APC）或细胞周期体介导[4,5]。当细胞退出有丝分裂时，APC对于末期后期有丝分裂周期蛋白的泛素依赖性降解也是必需的[6-9]。尽管磷酸化似乎参与其中[10]，但尚不清楚在后期开始时是什么激活了APC。在酿酒酵母中，染色体分离也需要CDC20基因，其产物包含WD40重复序列[11,12]。我们研究了APC与Cdc20蛋白之间的功能关系。我们提供的证据有力地表明，Cdc20是APC依赖性蛋白水解的关键调节因子，因此在没有Cdc20的情况下，细胞在后期开始时无法降解Pds1，在末期也无法降解有丝分裂周期蛋白Clb2。这一观点与我们的观察结果一致，即Cdc20定位于细胞核，并与APC组分Cdc23进行共免疫沉淀。
