The when and wheres of CDC25 phosphatases

The CDC25 phosphatases are key regulators of normal cell division and the cell's response to DNA damage. Earlier studies suggested non-overlapping roles for each isoform during a specific cell cycle phase. However, recent data suggest that multiple CDC25 isoforms cooperate to regulate each cell cycle transition. For instance, although CDC25A was initially thought to exclusively regulate the G 1–S transition, recent data demonstrate a significant role for CDC25A in the G 2–M transition. Further evidence demonstrates that in addition to the ATM/ATR–CHK pathway, a p38–MAPKAP pathway is also involved in controlling CDC25 activity during G 2/M checkpoint activation. Together with the fact that CDC25 overexpression is reported in many cancers, these data highlight the significance of developing specific CDC25 inhibitors for cancer therapy.