CDC25ABC

CDC25ABC refers to the family of CDC25 dual-specificity phosphatases, a set of enzymes that regulate cell cycle progression in eukaryotic cells. In humans, the CDC25 family comprises three closely related isoforms: CDC25A, CDC25B, and CDC25C. These enzymes share a common biochemical role but exhibit distinct expression patterns and functions during the cell cycle.

Functionally, CDC25 phosphatases activate cyclin-dependent kinases (CDKs) by removing inhibitory phosphates from CDKs such as CDK2 and CDK1. This dephosphorylation promotes the G1/S transition and the G2/M transition, enabling DNA replication and mitosis. Each isoform contributes to different phases of the cycle: CDC25A largely influences S-phase entry and early S-phase progression; CDC25B assists in G2/M entry and can act in multiple compartments; CDC25C is particularly important for mitotic entry. They often work with Cyclin partners (e.g., Cyclin E/A for CDK2, Cyclin B for CDK1) to drive progression.

Regulation of CDC25ABC is tight and multi-layered. They are controlled by checkpoint signaling in response to DNA damage or replication stress, notably through kinases such as Chk1 and Chk2, which phosphorylate CDC25 proteins to promote 14-3-3 protein binding and cytoplasmic sequestration or degradation. Phosphorylation events can modulate stability and localization, ensuring cells do not progress to mitosis with damaged DNA.

Clinical relevance centers on cell cycle control. Abnormal CDC25 expression or activity is associated with uncontrolled proliferation in various cancers, making CDC25 isoforms targets of interest for anti-cancer strategies. Research continues to elucidate isoform-specific roles and regulatory networks across species.

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