Proteasome-dependent degradation of human CDC25B phosphatase.
The CDC25 dual specificity phosphatase is a universal cell cycle regulator. The evolutionary conservation of this enzyme from yeast to man bears witness to its major role in the control of cyclin-dependent kinases (CDK) activity that are central regulators of the cell cycle machinery. CDC25 phosphatase both dephosphorylates and activates CDKs. Three human CDC25s have been identified. CDC25A is involved in the control of G1/S, and CDC25C at G2/M throught the activation of CDK 1-cyclin B. The exact function of CDC25B however remains elusive. We have found that CDC25B is degraded by the proteasome pathway in vitro and in vivo. This degradation is dependent upon phosphorylation by the CDK1-cyclin A complex, but not by CDK1-cyclin B. Together with the observations of others made in yeast and mammals, our results suggest that CDC25B might act as a 'mitotic starter' triggering the activation of an auto-amplification loop before being degraded.
Cans
C
C
Institut de Pharmacologie et de Biologie Structurale du CNRS and Université Paul Sabatier, Toulouse, France.
Ducommun
B
B
Baldin
V
V
D002453:Cell Cycle; D018797:Cell Cycle Proteins / Q000378:metabolism*; D003546:Cysteine Endopeptidases / Q000378:metabolism*; D006801:Humans; D008938:Mitosis; D009097:Multienzyme Complexes / Q000378:metabolism*; D010749:Phosphoprotein Phosphatases / Q000378:metabolism*; D010766:Phosphorylation; D046988:Proteasome Endopeptidase Complex; D020687:cdc25 Phosphatases
D018797:Cell Cycle Proteins; D009097:Multienzyme Complexes; D010749:Phosphoprotein Phosphatases; C517008:CDC25B protein, human; D020687:cdc25 Phosphatases; D003546:Cysteine Endopeptidases; D046988:Proteasome Endopeptidase Complex