Human Cdc25A phosphatase has a non-redundant function in G2 phase by activating Cyclin A-dependent kinases.
Cdc25 phosphatases activate Cdk/Cyclin complexes by dephosphorylation and thus promote cell cycle progression. We observed that the peak activity of Cdc25A precedes the one of Cdc25B in prophase and the maximum of Cyclin/Cdk kinase activity. Furthermore, Cdc25A activates both Cdk1-2/Cyclin A and Cdk1/Cyclin B complexes while Cdc25B seems to be involved only in activation of Cdk1/Cyclin B. Concomitantly, repression of Cdc25A led to a decrease in Cyclin A-associated kinase activity and attenuated Cdk1 activation. Our results indicate that Cdc25A acts before Cdc25B - at least in cancer cells, and has non-redundant functions in late G2/early M-phase as a major regulator of Cyclin A/kinase complexes.
Timofeev
Oleg
O
Cell Cycle Control and Carcinogenesis, German Cancer Research Center, Im Neuenheimer Feld 242, D-69120 Heidelberg, Germany.
Cizmecioglu
Onur
O
Hu
Entan
E
Orlik
Thomas
T
Hoffmann
Ingrid
I
D045744:Cell Line, Tumor; D019925:Cyclin A / Q000235:genetics / Q000378:metabolism*; D004789:Enzyme Activation; D005434:Flow Cytometry; D016195:G2 Phase / Q000502:physiology*; D006367:HeLa Cells; D006801:Humans; D018715:Microscopy, Video; D010770:Phosphotransferases / Q000235:genetics / Q000378:metabolism*; D020687:cdc25 Phosphatases / Q000235:genetics / Q000378:metabolism / Q000502:physiology*
D019925:Cyclin A; D010770:Phosphotransferases; D020687:cdc25 Phosphatases