14-3-3-PROTEINS ASSOCIATE WITH CDC25-PHOSPHATASES

The cdc25 phosphatases play key roles in cell cycle progression by act ivating cyclin-dependent kinases. Two members of the 14-3-3 protein fa mily have been isolated in a yeast two-hybrid screen designed to ident ify proteins that interact with the human cdc25A and cdc25B phosphatas es. Genes encoding the human homolog of the 14-3-3 epsilon protein and the previously described 14-3-3 beta protein have been isolated in th is screening. 14-3-3 proteins constitute a family of well-conserved eu karyotic proteins that were originally isolated in mammalian brain pre parations and that possess diverse biochemical activities related to s ignal transduction. We present evidence that indicates that cdc25 and 14-3-3 proteins physically interact both in vitro and in vivo. 14-3-3 protein does not, however, affect the phosphatase activity of cdc25A. Raf-1, which is known to bind 14-3-3 proteins, has recently been shown to associate with cdc25A and to stimulate its phosphatase activity. 1 4-3-3 protein, however,has no effect on the cdc25A-kinase activity of Raf-1. Instead, 14-3-3 may facilitate the association of cdc25 with Ra f-1 in vivo, participating in the linkage between mitogenic signaling and the cell cycle machinery.