Schneider B L, Patton E E, Lanker S, Mendenhall M D, Wittenberg C, Futcher B, Tyers M
Cold Spring Harbor Laboratory, New York 11724, USA.
Nature. 1998 Sep 3;395(6697):86-9. doi: 10.1038/25774.
In most eukaryotes, commitment to cell division occurs in late G1 phase at an event called Start in the yeast Saccharomyces cerevisiae, and called the restriction point in mammalian cells. Start is triggered by the cyclin-dependent kinase Cdc28 and three rate-limiting activators, the G1 cyclins Cln1, Cln2 and Cln3. Cyclin accumulation in G1 is driven in part by the cell-cycle-regulated transcription of CLN1 and CLN2, which peaks at Start. CLN transcription is modulated by physiological signals that regulate G1 progression, but it is unclear whether Cln protein stability is cell-cycle-regulated. It has been suggested that once cells pass Start, Cln proteolysis is triggered by the mitotic cyclins Clb1, 2, 3 and 4. But here we show that G1 cyclins are unstable in G1 phase, and that Clb-Cdc28 activity is not needed fgr G1 cyclin turnover. Cln instability thus provides a means to couple Cln-Cdc28 activity to transcriptional regulation and protein synthetic rate in pre-Start G1 cells.
在大多数真核生物中,细胞进入分裂期的决定发生在G1期晚期,在酿酒酵母中这一事件称为“起始点”,在哺乳动物细胞中则称为“限制点”。“起始点”由细胞周期蛋白依赖性激酶Cdc28以及三种限速激活因子(即G1期细胞周期蛋白Cln1、Cln2和Cln3)触发。G1期细胞周期蛋白的积累部分是由CLN1和CLN2的细胞周期调控转录驱动的,其转录高峰出现在“起始点”。CLN转录受调节G1期进程的生理信号调控,但尚不清楚Cln蛋白稳定性是否受细胞周期调控。有人提出,一旦细胞通过“起始点”,有丝分裂细胞周期蛋白Clb1、2、3和4会触发Cln蛋白水解。但我们在此表明,G1期细胞周期蛋白在G1期不稳定,且Clb - Cdc28活性对于G1期细胞周期蛋白的周转并非必需。因此,Cln的不稳定性为将Cln - Cdc28活性与“起始点”前G1期细胞中的转录调控及蛋白质合成速率相联系提供了一种方式。