Cdc25fosfataser

Cdc25 fosfataser, often written as Cdc25 phosphatases in English, are a family of dual-specificity protein phosphatases that regulate cell cycle progression in eukaryotic cells by activating cyclin-dependent kinases (CDKs). They achieve this primarily by dephosphorylating inhibitory phosphates on CDKs, particularly at Tyr15 and, in some contexts, Thr14, thereby enabling entry into mitosis or S phase depending on the isoform and cellular context.

In humans, the CDC25 family includes CDC25A, CDC25B, and CDC25C, with overlapping but distinct roles. CDC25A mainly promotes the G1/S transition by activating CDK2, while CDC25B and CDC25C promote the G2/M transition by activating CDK1/cyclin B, with CDC25C playing a key role in mitotic entry. In yeast, Cdc25 homologs perform similar regulatory functions, indicating a conserved role in coordinating cell cycle progression.

Biochemically, CDC25 enzymes are dual-specificity phosphatases containing a catalytic HCX5R motif in their active site and can act on multiple CDKs. Regulation is multifaceted: DNA damage–responsive kinases (such as ATM/ATR and Chk1/Chk2) can phosphorylate CDC25 proteins, promoting 14-3-3–mediated cytoplasmic sequestration or targeting them for degradation, thereby preventing CDK activation. Subcellular localization, phosphorylation state, and protein interactions modulate their activity during the cell cycle.

Dysregulation of CDC25 proteins is associated with cancer, where overexpression or aberrant regulation can drive unchecked proliferation. As a result, CDC25s are explored as potential therapeutic targets, and several inhibitors have been investigated in preclinical models, though achieving high specificity remains a challenge.