CDC25B

CDC25B is a human protein encoded by the CDC25B gene and a member of the CDC25 family of dual-specificity phosphatases. The CDC25 enzymes activate cyclin-dependent kinases by removing inhibitory phosphates from CDKs, thereby promoting cell cycle progression. CDC25B is primarily involved in triggering the G2/M transition and also contributes to S-phase progression by activating CDK1 and CDK2 in coordination with their cyclins. The protein contains a catalytic phosphatase domain and regulatory regions that govern its activity and localization, with shuttling between the nucleus and cytoplasm depending on the cell cycle stage and signaling cues.

Regulation of CDC25B activity integrates signals from growth factors, cell cycle controls, and DNA damage responses. Phosphorylation and interactions with 14-3-3 proteins modulate its localization and activity. In response to DNA damage, the ATR/ATM–CHK1/CHK2 pathways lead to phosphorylation of CDC25B, promoting 14-3-3 binding and cytoplasmic sequestration or degradation, which prevents premature mitotic entry. This checkpoint mechanism helps preserve genomic integrity.

Clinical significance of CDC25B lies in its association with uncontrolled cell proliferation when dysregulated. Overexpression or altered regulation of CDC25B has been observed in various cancers, making CDC25 family members potential targets for therapeutic intervention. Research has explored small-molecule inhibitors and other strategies to modulate CDC25B activity as part of anti-cancer approaches.

See also CDC25A; CDC25C; cell cycle regulation.