Correa-Bordes J, Gulli M P, Nurse P
Cell Cycle Laboratory, Imperial Cancer Research Fund, London, UK.
EMBO J. 1997 Aug 1;16(15):4657-64. doi: 10.1093/emboj/16.15.4657.
The fission yeast Schizosaccharomyces pombe CDK inhibitor p25rum1 plays a major role in regulating cell cycle progression during G1. Here we show that p25rum1 associates with the CDK p34cdc2/p56cdc13 during G1 in normally cycling cells and is required for the rapid proteolysis of p56cdc13. In vitro binding data indicate that p25rum1 has specificity for the B-cyclin p56cdc13 component of the CDK and can bind the cyclin even in the absence of the cyclin destruction box. At the G1-S-phase transition, p25rum1 levels decrease and p56cd13 levels increase. We also show that on release from a G1 block, the rapid disappearance of p25rum1 requires the activity of the CDK p34cdc2/cig1p and that this same CDK phosphorylates p25rum1 in vitro. We propose that the binding of p25rum1 to p56cdc13 promotes cyclin proteolysis during G1, with p25rum1 possibly acting as an adaptor protein, promoting transfer of p56cdc13 to the proteolytic machinery. At the G1-S-phase transition, p25rum1 becomes targeted for proteolysis by a mechanism which may involve p34cdc2/cig1p phosphorylation. As a consequence, at this point in the cell cycle p56cdc13 proteolysis is inhibited, leading to a rise of p56cdc13 levels in preparation for mitosis.
裂殖酵母粟酒裂殖酵母的细胞周期蛋白依赖性激酶（CDK）抑制剂p25rum1在G1期调控细胞周期进程中起主要作用。我们在此表明，在正常循环的细胞中，p25rum1在G1期与CDK p34cdc2/p56cdc13结合，并且是p56cdc13快速蛋白水解所必需的。体外结合数据表明，p25rum1对CDK的B型细胞周期蛋白p56cdc13组分具有特异性，甚至在没有细胞周期蛋白破坏框的情况下也能结合细胞周期蛋白。在G1-S期转变时，p25rum1水平下降而p56cd13水平上升。我们还表明，从G1期阻滞释放后，p25rum1的快速消失需要CDK p34cdc2/cig1p的活性，并且相同的CDK在体外使p25rum1磷酸化。我们提出，p25rum1与p56cdc13的结合在G1期促进细胞周期蛋白的蛋白水解，p25rum1可能作为衔接蛋白，促进p56cdc13向蛋白水解机制的转移。在G1-S期转变时，p25rum1通过一种可能涉及p34cdc2/cig1p磷酸化的机制成为蛋白水解的靶点。因此，在细胞周期的这一时刻，p56cdc13的蛋白水解受到抑制，导致p56cdc13水平升高以准备有丝分裂。
