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.
Boutros
Rose
R
LBCMCP-CNRS UMR5088, IFR109, Université Paul Sabatier, 118 route de Narbonne, 31062 Toulouse, France.
Dozier
Christine
C
Ducommun
Bernard
B
D000818:Animals; D016227:Benzoquinones / Q000627:therapeutic use; D002453:Cell Cycle / Q000502:physiology*; D018797:Cell Cycle Proteins / Q000378:metabolism / Q000502:physiology; D006801:Humans; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000502:physiology; D008954:Models, Biological; D009285:Naphthoquinones / Q000627:therapeutic use; D009369:Neoplasms / Q000188:drug therapy / Q000201:enzymology; D015363:Quinolones / Q000627:therapeutic use; D011809:Quinones / Q000627:therapeutic use; D013844:Thiazoles / Q000627:therapeutic use; D020687:cdc25 Phosphatases / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000502:physiology*
C451261:2,3-bis(2-hydroxyethylsulfanyl)-(1,4)naphthoquinone; C506607:BN 82685; D016227:Benzoquinones; D018797:Cell Cycle Proteins; D007527:Isoenzymes; C440614:NSC 663284; D009285:Naphthoquinones; D015363:Quinolones; D011809:Quinones; D013844:Thiazoles; D020687:cdc25 Phosphatases