CDC25 phosphatases in cancer cells: key players? Good targets?

Abstract

Cell division cycle 25 (CDC25) phosphatases regulate key transitions between cell cycle phases during normal cell division, and in the event of DNA damage they are key targets of the checkpoint machinery that ensures genetic stability. Taking only this into consideration, it is not surprising that CDC25 overexpression has been reported in a significant number of human cancers. However, in light of the significant body of evidence detailing the stringent complexity with which CDC25 activities are regulated, the significance of CDC25 overexpression in a subset of cancers and its association with poor prognosis are proving difficult to assess. We will focus on the roles of CDC25 phosphatases in both normal and abnormal cell proliferation, provide a critical assessment of the current data on CDC25 overexpression in cancer, and discuss both current and future therapeutic strategies for targeting CDC25 activity in cancer treatment.

Protein kinase a modulates Cdc25B activity during meiotic resumption of mouse oocytes

“…The distinct N-terminal domains of the three Cdc25 phosphatases suggest that these phosphatases have different functions in cell cycle regulation. Cdc25A controls both G 1 /S and G 2 /M transition and Cdc25B is implicated in both the G 2 /M transition and S phase progression, whereas Cdc25C promotes the G 2 /M transition (Nilsson and Hoffmann, 2000;Boutros et al, 2006Boutros et al, , 2007Rudolph, 2007). Oocytes from cdc25b Ϫ/Ϫ mice are unable to resume meiosis and remain arrested in prophase unless rescued by microinjection of Cdc25B mRNA.…”

The natural anticancer compound rocaglamide selectively inhibits the G1-S-phase transition in cancer cells through the ATM/ATR-mediated Chk1/2 cell cycle checkpoints

“…Cancer cells are characterized by deregulation in the cell division cycle, which is associated with increased DNA replication and elevated cellular proliferation. [1][2][3] Therefore, targeting the cancer cell cycle machinery has been considered to be a rational strategy for cancer treatment. 4 Cell division is governed by cyclin dependent kinases (CDKs) that are tightly regulated by cyclins and CDK inhibitors (CDKIs).…”

“…2 Moreover, elevated expressions of the cell division cycle 25 (Cdc25) phosphatases, in particular, the isoform Cdc25A, which is essential for cell cycle transitions of G1-S and S-G2, has been shown in different cancers and their over-expression often correlates with more aggressive disease and poor prognosis. 1,5 Recently, genetic studies indicate that CDK2, CDK4 and CDK6 are not essential for the mammalian cell cycle. Instead, they are only required for the proliferation of specific cell types.…”

Mangrove dolabrane‐type of diterpenes tagalsins suppresses tumor growth viaROS‐mediated apoptosis and ATM/ATR–Chk1/Chk2‐regulated cell cycle arrest

“…5 a ). Chk1 and Chk2 are the cell cycle checkpoint kinases downstream of ATM and ATR 21, 23. Chk1 and Chk2 were shown to be phosphorylated at the Ser317 and Thr68 site, respectively (Fig.…”

“…5 a ). Chk1 and Chk2 are known to regulate the stability of the cell division cycle phosphatases 25A (Cdc25A) and Cdc25B 21, 23. TC treatment was shown to induce phosphorylation of Cdc25A at the Ser178 site, and, consequently, degradation (Fig.…”