Cell division cycle 25 phosphatase (CDC25)

Cell division cycle 25 (CDC25) phosphatases are a family of dual-specificity phosphatases that play a critical role in regulating the eukaryotic cell cycle (Boutros et al., 2007). They function by removing inhibitory phosphate groups from threonine and tyrosine residues of cyclin-dependent kinases (CDKs), thereby activating the CDK/cyclin complexes necessary for cell cycle progression (Kristjansdottir and Rudolph, 2004). In humans, three isoforms exist: CDC25A, which regulates the G1/S and G2/M transitions; CDC25B, which initiates the G2/M transition; and CDC25C, which maintains the G2/M transition (UniProt P30304, P30305, P30307). Overexpression of CDC25 isoforms is frequently observed in a wide range of human cancers, including breast, lung, and colorectal cancers, and is often correlated with poor prognosis (Boutros et al., 2007). Consequently, CDC25 phosphatases are considered significant therapeutic targets for cancer treatment. Small molecule inhibitors designed to target the catalytic site or allosteric sites of CDC25 aim to induce cell cycle arrest and subsequent apoptosis in malignant cells (Lavecchia et al., 2010). Despite their potential, the development of clinically viable CDC25 inhibitors has been hindered by challenges such as poor bioavailability, lack of isoform selectivity, and the highly reactive nature of many early-stage inhibitors (Brezak et al., 2008). Research continues to focus on developing more selective and stable inhibitors to minimize off-target effects and improve therapeutic efficacy (Lavecchia et al., 2010).

Other names

M-phase inducer phosphataseCDC25ACDC25BCDC25CDual-specificity phosphatase CDC25M-phase inducer phosphatase 1M-phase inducer phosphatase 2M-phase inducer phosphatase 3

Inhibition of the phosphatase activity of CDC25, preventing the dephosphorylation and activation of Cyclin-Dependent Kinases (CDKs), which results in cell cycle arrest at G1/S or G2/M phases.