Huang J N, Park I, Ellingson E, Littlepage L E, Pellman D
Department of Pediatric Oncology, The Dana-Farber Cancer Institute, Harvard Medical School, 44 Binney Street, Boston, MA 02115, USA.
J Cell Biol. 2001 Jul 9;154(1):85-94. doi: 10.1083/jcb.200102007.
Cell cycle progression is driven by waves of cyclin expression coupled with regulated protein degradation. An essential step for initiating mitosis is the inactivation of proteolysis mediated by the anaphase-promoting complex/cyclosome (APC/C) bound to its regulator Cdh1p/Hct1p. Yeast APC(Cdh1) was proposed previously to be inactivated at Start by G1 cyclin/cyclin-dependent kinase (CDK). Here, we demonstrate that in a normal cell cycle APC(Cdh1) is inactivated in a graded manner and is not extinguished until S phase. Complete inactivation of APC(Cdh1) requires S phase cyclins. Further, persistent APC(Cdh1) activity throughout G1 helps to ensure the proper timing of Cdc20p expression. This suggests that S phase cyclins have an important role in allowing the accumulation of mitotic cyclins and further suggests a regulatory loop among S phase cyclins, APC(Cdh1), and APC(Cdc20).
细胞周期进程由细胞周期蛋白表达的波动以及受调控的蛋白质降解驱动。启动有丝分裂的一个关键步骤是与调节因子Cdh1p/Hct1p结合的后期促进复合物/细胞周期体（APC/C）介导的蛋白水解失活。先前有人提出酵母APC（Cdh1）在起始点被G1期细胞周期蛋白/细胞周期蛋白依赖性激酶（CDK）失活。在这里，我们证明在正常细胞周期中，APC（Cdh1）以分级方式失活，直到S期才完全失活。APC（Cdh1）的完全失活需要S期细胞周期蛋白。此外，整个G1期持续的APC（Cdh1）活性有助于确保Cdc20p表达的正确时间。这表明S期细胞周期蛋白在允许有丝分裂细胞周期蛋白积累方面具有重要作用，并且进一步表明在S期细胞周期蛋白、APC（Cdh1）和APC（Cdc20）之间存在一个调节环。
