Listovsky T, Zor A, Laronne A, Brandeis M
Department of Genetics, The Institute of Life Sciences, The Hebrew University of Jerusalem, Jerusalem, 91904, Israel.
Exp Cell Res. 2000 Mar 15;255(2):184-91. doi: 10.1006/excr.1999.4788.
The cyclosome/APC (anaphase-promoting complex), the major component of cell-cycle-specific ubiquitin-mediated proteolysis of mitotic cyclins and of other cell cycle proteins, is essential for sister chromatid separation and for exit from mitosis. Cyclosome activity and substrate specificity are modulated by phosphorylation and by transient interactions with Fizzy/cdc20 (Fzy) and Fizzy-related/Hct1/Cdh1 (Fzr). This regulation has been studied so far in Drosophila embryos, in yeast, and in cell-free extracts in vitro. Studying cyclosome regulation in mammalian cells in vivo we found that both Fzr overexpression and Cdk1 inhibition can override the prometaphase checkpoint. We further show that Fzr activation of the cyclosome is negatively regulated by Cdk1. Finally, we show that the mammalian cdc14 phosphatase, like its budding yeast homologue, plays a role in cyclosome pathway regulation. These results suggest that Cdk1 is essential for coupling various activities of the cyclosome and in particular for preventing Fzr from short-circuiting the spindle pole checkpoint. Cdk1-cyclin B is thus an inhibitor, activator, and substrate of the cyclosome.
细胞周期体/后期促进复合物（APC）是有丝分裂周期蛋白和其他细胞周期蛋白的细胞周期特异性泛素介导的蛋白水解的主要成分，对姐妹染色单体分离和退出有丝分裂至关重要。细胞周期体活性和底物特异性受磷酸化以及与Fizzy/cdc20（Fzy）和Fizzy相关蛋白/Hct1/Cdh1（Fzr）的瞬时相互作用调节。迄今为止，已在果蝇胚胎、酵母和体外无细胞提取物中研究了这种调节。在体内研究哺乳动物细胞中的细胞周期体调节时，我们发现Fzr过表达和Cdk1抑制均可越过前中期检查点。我们进一步表明，细胞周期体的Fzr激活受Cdk1负调控。最后，我们表明哺乳动物的cdc14磷酸酶与其芽殖酵母同源物一样，在细胞周期体途径调节中起作用。这些结果表明，Cdk1对于耦合细胞周期体的各种活性至关重要，特别是对于防止Fzr使纺锤体极检查点短路。因此，Cdk1-细胞周期蛋白B是细胞周期体的抑制剂、激活剂和底物。
