M-phase inducer phosphatase (CDC25)

M-phase inducer phosphatase, widely known as the CDC25 family (comprising CDC25A, CDC25B, and CDC25C), consists of dual-specificity phosphatases that are essential regulators of the eukaryotic cell cycle [UniProt P30304, P30305, P30307]. These enzymes catalyze the removal of inhibitory phosphate groups from highly conserved threonine and tyrosine residues within cyclin-dependent kinases (CDKs), such as CDK1 and CDK2, thereby activating the CDK/cyclin complexes required for progression through various cell cycle checkpoints [PMID: 15613418]. CDC25A primarily regulates the G1/S and S phase transitions, while CDC25B and CDC25C are critical for the G2/M transition and entry into mitosis [PMID: 28651534]. Due to their pivotal role in driving cell division, CDC25 phosphatases are frequently overexpressed in a wide range of human malignancies, including breast, lung, and colorectal cancers, where their high expression often correlates with aggressive tumor behavior and poor clinical outcomes [PMID: 28651534]. As such, they have emerged as significant therapeutic targets for the development of anti-cancer agents designed to induce cell cycle arrest and apoptosis in tumor cells. Despite their potential, the clinical advancement of CDC25 inhibitors has been hindered by challenges such as the high reactivity of the active site cysteine, poor selectivity among isoforms, and significant systemic toxicities, particularly affecting rapidly dividing normal tissues like the bone marrow [PMID: 28651534].

Other names

Cell division cycle 25CDC25 familyDual specificity phosphatase CDC25M-phase inducer phosphatase 1 (CDC25A)M-phase inducer phosphatase 2 (CDC25B)M-phase inducer phosphatase 3 (CDC25C)

Inhibition of the dephosphorylation of Cyclin-Dependent Kinases (CDKs), specifically at inhibitory threonine and tyrosine residues (Thr-14 and Tyr-15), which prevents the activation of CDK/cyclin complexes and results in cell cycle arrest at G1/S or G2/M phases [PMID: 15613418, PMID: 28651534].