Phosphorylation Mediated Regulation of Cdc25 Activity, Localization and Stability

Dual specificity phosphatases of the Cdc25 family are critically important regulators of the cell cycle. They activate cyclin-dependent kinases (CDKs) at key cell cycle transitions such as the initiation of DNA synthesis and mitosis. They also represent key points of regulation for pathways monitoring DNA integrity, DNA replication, growth factor signaling and extracellular stress. Since their mis-regulation allows cells to function in a genetically unstable state, it is not surprising that these phosphatases are involved in transformation to a cancerous state. Cdc25 phosphatases are heavily regulated by phosphorylation. Many regulatory phosphorylation sites on Cdc25 influence catalytic activity, substrate specificity, subcellular localization and stability. This chapter summarizes the current literature on the phospho-regulation of these proteins.