p25rum1 promotes proteolysis of the mitotic B-cyclin p56cdc13 during G1 of the fission yeast cell cycle.
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.
Correa-Bordes
J
J
Cell Cycle Laboratory, Imperial Cancer Research Fund, London, UK.
Gulli
M P
MP
Nurse
P
P
D016203:CDC2 Protein Kinase / Q000378:metabolism; D019926:Cyclin B; D016213:Cyclins / Q000378:metabolism*; D010450:Endopeptidases / Q000378:metabolism; D005656:Fungal Proteins / Q000378:metabolism*; D016193:G1 Phase / Q000502:physiology*; D007700:Kinetics; D008938:Mitosis / Q000502:physiology; D010766:Phosphorylation; D011485:Protein Binding; D012568:Schizosaccharomyces / Q000166:cytology* / Q000378:metabolism*; D029702:Schizosaccharomyces pombe Proteins
C095858:Cig1 protein, S pombe; D019926:Cyclin B; D016213:Cyclins; D005656:Fungal Proteins; C086077:Rum1 protein, S pombe; D029702:Schizosaccharomyces pombe Proteins; D016203:CDC2 Protein Kinase; D010450:Endopeptidases