Yamaguchi S, Murakami H, Okayama H
Department of Biochemistry, Faculty of Medicine, The University of Tokyo, Hongo, Tokyo 113, Japan.
Mol Biol Cell. 1997 Dec;8(12):2475-86. doi: 10.1091/mbc.8.12.2475.
In the fission yeast Schizosaccharomyces pombe, p34(cdc2) plays a central role controlling the cell cycle. We recently isolated a new gene named srw1(+), capable of encoding a WD repeat protein, as a multicopy suppressor of hyperactivated p34(cdc2). Cells lacking srw1(+) are sterile and defective in cell cycle controls. When starved for nitrogen source, they fail to effectively arrest in G1 and die of accelerated mitotic catastrophe if regulation of p34(cdc2)/Cdc13 by inhibitory tyrosine phosphorylation is compromised by partial inactivation of Wee1 kinase. Fertility is restored to the disruptant by deletion of Cig2 B-type cyclin or slight inactivation of p34(cdc2). srw1(+) shares functional similarity with rum1(+), having abilities to induce endoreplication and restore fertility to rum1 disruptants. In the srw1 disruptant, Cdc13 fails to be degraded when cells are starved for nitrogen. We conclude that Srw1 controls differentiation and cell cycling at least by negatively regulating Cig2- and Cdc13-associated p34(cdc2) and that one of its roles is to down-regulate the level of the mitotic cyclin particularly in nitrogen-poor environments.
在裂殖酵母粟酒裂殖酵母中，p34(cdc2)在控制细胞周期方面发挥着核心作用。我们最近分离出一个名为srw1(+)的新基因，它能够编码一种WD重复蛋白，作为过度激活的p34(cdc2)的多拷贝抑制因子。缺乏srw1(+)的细胞是不育的，并且在细胞周期控制方面存在缺陷。当缺乏氮源时，如果Wee1激酶部分失活导致抑制性酪氨酸磷酸化对p34(cdc2)/Cdc13的调节受损，它们就无法有效地停滞在G1期，并死于加速的有丝分裂灾难。通过缺失Cig2 B型细胞周期蛋白或使p34(cdc2)轻微失活，可恢复突变体的育性。srw1(+)与rum1(+)具有功能相似性，具有诱导核内复制和恢复rum1突变体育性的能力。在srw1突变体中，当细胞缺乏氮源时，Cdc13无法降解。我们得出结论，Srw1至少通过负向调节与Cig2和Cdc13相关的p34(cdc2)来控制分化和细胞周期，并且其作用之一是特别是在氮缺乏的环境中下调有丝分裂细胞周期蛋白的水平。
