Phosphorylation of human CDC25B phosphatase by CDK1-cyclin A triggers its proteasome-dependent degradation.
In eukaryotes the activity of CDK1 (CDC2), a cyclin-dependent kinase that initiates the structural changes that culminate in the segregation of chromosomes at mitosis, is regulated by the synergistic and opposing activities of a cascade of kinases and phosphatases. Dephosphorylation of threonine 14 and tyrosine 15 of CDK1 by the CDC25 phosphatases is a key step in the activation of the CDK1-cyclin B protein kinase. Little is currently known about the role and the regulation of CDC25B. Here we report in vitro and in vivo data that indicate that CDC25B is degraded by the proteasome. This degradation is dependent upon phosphorylation by the CDK1-cyclin A complex but not by CDK1-cyclin B. These results indicate that CDK1-cyclin A phosphorylation targets CDC25B for degradation and that this might be an important component of cell cycle regulation at the G2/M transition.
Baldin
V
V
Institut de Pharmacologie et de Biologie Structurale du CNRS, Université Paul Sabatier, 205 route de Narbonne, 31077 Toulouse cedex, France.
Cans
C
C
Knibiehler
M
M
Ducommun
B
B
D016203:CDC2 Protein Kinase / Q000378:metabolism*; D002154:Calpain / Q000037:antagonists & inhibitors; D002453:Cell Cycle; D018797:Cell Cycle Proteins / Q000378:metabolism*; D019925:Cyclin A / Q000378:metabolism*; D003546:Cysteine Endopeptidases / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D007976:Leupeptins / Q000494:pharmacology; D009097:Multienzyme Complexes / Q000378:metabolism*; D010749:Phosphoprotein Phosphatases / Q000378:metabolism*; D010766:Phosphorylation; D046988:Proteasome Endopeptidase Complex; D013912:Threonine / Q000378:metabolism; D014443:Tyrosine / Q000378:metabolism; D020687:cdc25 Phosphatases
D018797:Cell Cycle Proteins; D019925:Cyclin A; D007976:Leupeptins; D009097:Multienzyme Complexes; C063261:acetylleucyl-leucyl-norleucinal; D013912:Threonine; D014443:Tyrosine; D016203:CDC2 Protein Kinase; D010749:Phosphoprotein Phosphatases; C517008:CDC25B protein, human; D020687:cdc25 Phosphatases; D002154:Calpain; D003546:Cysteine Endopeptidases; D046988:Proteasome Endopeptidase Complex