Schwob E, Böhm T, Mendenhall M D, Nasmyth K
I. M. P. Research Institute of Molecular Pathology, Vienna, Austria.
Cell. 1994 Oct 21;79(2):233-44. doi: 10.1016/0092-8674(94)90193-7.
When yeast cells reach a critical size, they initiate bud formation, spindle pole body duplication, and DNA replication almost simultaneously. All three events depend on activation of Cdc28 protein kinase by the G1 cyclins Cln1, -2, and -3. We show that DNA replication also requires activation of Cdc28 by B-type (Clb) cyclins. A sextuple clb1-6 mutant arrests as multibudded G1 cells that resemble cells lacking the Cdc34 ubiquitin-conjugating enzyme. cdc34 mutants cannot enter S phase because they fail to destroy p40SIC1, which is a potent inhibitor of Clb but not Cln forms of the Cdc28 kinase. In wild-type cells, p40SIC1 protein appears at the end of mitosis and disappears shortly before S phase. Proteolysis of a cyclin-specific inhibitor of Cdc28 is therefore an essential aspect of the G1 to S phase transition.
当酵母细胞达到临界大小时，它们几乎同时启动芽的形成、纺锤极体复制和DNA复制。这三个事件均依赖于G1细胞周期蛋白Cln1、-2和-3对Cdc28蛋白激酶的激活作用。我们发现，DNA复制还需要B型（Clb）细胞周期蛋白对Cdc28的激活。六倍体clb1-6突变体停滞为多芽的G1细胞，类似于缺乏Cdc34泛素结合酶的细胞。cdc34突变体无法进入S期，因为它们无法降解p40SIC1，p40SIC1是Cdc28激酶的Clb形式而非Cln形式的有效抑制剂。在野生型细胞中，p40SIC1蛋白出现在有丝分裂末期，并在S期前不久消失。因此，对Cdc28的细胞周期蛋白特异性抑制剂进行蛋白水解是G1期到S期转换的一个重要方面。
