Eukaryotic Cell Cycle Control

本研究的目的是了解控制细胞周期“启动”和细胞分化“启动”的分子机制。为此，裂变酵母作为一种模式生物被研究，因为这种生物与高等真核生物密切相关。在过去的3年中，我们发现了4个控制分化开始的新因子和5个控制细胞周期“开始”的新因子。在这4个因子中，b型细胞周期蛋白负向控制分化的开始，正向控制细胞周期的开始；一种称为Phh1的应激信号MAP激酶，积极控制分化的开始；一种名为Rcd1的新蛋白质，它对氮饥饿诱导的分化开始至关重要；Nrd1，一种负向控制分化开始的RNA结合蛋白。它们有哺乳动物同源物，提高了在裂变酵母中发现的分化控制系统可能保守到哺乳动物的可能性。5个细胞周期“开始”因子包括：与Cdc10形成转录因子复合物的DNA结合亚基Res2；Rep1和Rep2，两个转录激活子亚基，通过与Res2-Cdc10形成复合物而起作用；与Cdc2激酶结合并激活Res2/Cdc10/Rep2的新细胞周期蛋白Pas1；Spt1是一种结合Cdc18的新因子，对S期的发生和发展起着关键的控制作用。Spt1可能形成一个独立于Cdc2/Pas1-Res/Cdc10/Rep-Cdc18级联的控制级联。

The goal of this research is to understand the molecular mechanism controlling the cell cycle "start" and the cell differentiation "start". To this end, fission yeast has been studied as a model organism because this organism is closely related to higher eukaryotes. During the past 3 years, we have discovered 4 novel factors controlling the onset of differentiation and 5 new factors controlling the cell cycle "start". Among the 4 factors are a B-type cyclin that negatively controls the onset of differentiation and positively controls the start of the cell cycle ; a stress signal MAP kinase called Phh1 that positively controls the onset of differentiation ; a novel protein named Rcd1 that is essential for nitrogen-starvation-induced start of differentiation ; Nrd1, a RNA binding protein that negatively controls the onset of differentiation. They have mammalian homologues, raising the possibility that the differentiation control system found in fission yeast may be conserved up to mammals.Among the 5 cell cycle "start" factors are Res2, a DNA binding subunit that forms a transcriptional factor complex with Cdc10 ; Rep1 and Rep2, two transcriptional activator subunits that act by forming a complex with Res2-Cdc10 ; the new cyclin Pas1 that associates with Cdc2 kinase and activates Res2/Cdc10/Rep2 ; Spt1 a novel factor that binds Cdc18 and critically controls the onset and progression of S phase. Spt1 might form a control cascade independent of the Cdc2/Pas1-Res/Cdc10/Rep-Cdc18 cascade.