CDC25A: A Rebel Within the CDC25 Phosphatases Family?

CDC25 dual specificity phosphatases activate the cyclin-dependent kinase complexes, allowing timely ordered progression through out the different phases of the eukaryotic cell cycle. In humans, there are three genes coding for the CDC25A, B and C proteins with both different and redundant specificities and regulations. The CDC25A member of this family acts during the G1 phase and at the G1/S transition by activating the CDK2/cyclin E and CDK2/cyclin A complexes, a function apparently not shared by the other members. In consequence, CDC25A is submitted to extra-cellular signals-dependent regulations involving in particular mitogenic signal transducers, and leading to modifications of its stability, its localization or its activity. In addition, CDC25A is up-regulated in various cancers, and the molecular mechanisms leading to this up-regulation are far from being understood. In this review, we will synthesize the current knowledge about CDC25A molecular regulations, and try to integrate these data in the cell proliferation and apoptotic functions described for the protein.