THE CDC25B PHOSPHATASE IS ESSENTIAL FOR THE G2 M PHASE-TRANSITION IN HUMAN-CELLS/

Cdc25 phosphatases play key roles in cell cycle progression by activat ing cyclin-dependent kinases, In human cells, cdc25 proteins are encod ed by a multigene family, consisting of cdc25A, cdc25B and cdc25C, Whi le cdc25A plays a crucial role at the G(1)/S phase transition, cdc25C is involved in the dephosphorylation and activation of the mitotic kin ase, cdc2/cyclinB. In addition, cdc25C itself is regulated by cdc2/cyc linB which then creates a positive feedback loop that controls entry i nto mitosis, In this study we show that the activity of cdc25B appears during late S phase and peaks during G(2) phase. Both in vitro and in vivo cdc25B is activated through phosphorylation during S-phase. Usin g a cell duplication, microinjection assay we show that ablation of cd c25B function by specific antibodies blocks cell cycle progression in Hs68 cells by inhibition of entry into mitosis, Cdc25B function neithe r plays a role in later stages of mitosis nor for the inititation of D NA replication, These results indicate that cdc25B is a mitotic regula tor that might act as a 'starter phosphatase' to initiate the positive feedback loop at the entry into M phase.