Sánchez-Díaz A, González I, Arellano M, Moreno S
Instituto de Microbiología Bioquímica, CSIC/Universidad de Salamanca, Edificio Departamental, Campus Miguel de Unamuno, Salamanca, Spain.
J Cell Sci. 1998 Mar;111 ( Pt 6):843-51. doi: 10.1242/jcs.111.6.843.
p25rum1 and p40SIC1 are specific inhibitors of p34(cdc2/CDC28) kinase complexes with B-type cyclins that play a central role in the regulation of the G1 phase of the cell cycle. We show here that low levels of expression of SIC1 in Schizosaccharomyces pombe rescues all the phenotypes of cells lacking the rum1+ gene. In addition, high level expression of SIC1 in S. pombe induces extra rounds of DNA replication without mitosis, a phenotype very similar to the overexpression of rum1+. Transient expression of rum1+ in S. cerevisiae restores the G1 arrest phenotype of cdc4 sic1Delta double mutants. Overproduction of rum1+ in Saccharomyces cerevisiae causes a cell cycle block in G1 with a phenotype similar to inactivation of all the Clb cyclins. Finally, we have mapped the cyclin interacting domain and Cdk inhibitory domain to a region of about 80 amino acids in p25rum1 that has significant homology to the C-terminal domain of p40SIC1. All these observations suggest that fission yeast p25rum1 and budding yeast p40SIC1 define a family of Cdk inhibitors that specifically down regulate cyclin B/Cdk1 during the G1 phase of the cell cycle.
p25rum1和p40SIC1是p34(cdc2/CDC28)激酶复合物与B型细胞周期蛋白的特异性抑制剂，这些激酶复合物在细胞周期G1期的调控中起核心作用。我们在此表明，粟酒裂殖酵母中SIC1的低水平表达挽救了缺乏rum1+基因的细胞的所有表型。此外，粟酒裂殖酵母中SIC1的高水平表达诱导了无有丝分裂的额外几轮DNA复制，这一表型与rum1+的过表达非常相似。酿酒酵母中rum1+的瞬时表达恢复了cdc4 sic1Delta双突变体的G1期停滞表型。酿酒酵母中rum1+的过量产生导致细胞周期在G1期阻滞，其表型类似于所有Clb细胞周期蛋白失活。最后，我们已将细胞周期蛋白相互作用结构域和Cdk抑制结构域定位到p25rum1中约80个氨基酸的区域，该区域与p40SIC1的C末端结构域具有显著同源性。所有这些观察结果表明，裂殖酵母p25rum1和芽殖酵母p40SIC1定义了一类Cdk抑制剂家族，它们在细胞周期的G1期特异性下调细胞周期蛋白B/Cdk1。
