Cell division cycle 25A (CDC25A) (CDC25A)

Cell division cycle 25A (CDC25A) is a dual-specificity phosphatase that serves as a master regulator of the eukaryotic cell cycle by activating cyclin-dependent kinases (CDKs) (UniProt P30304). It functions by removing inhibitory phosphate groups from CDK4 and CDK6 during the G1 phase and CDK2 at the G1/S transition, thereby promoting entry into the S phase (GeneCards). Additionally, it dephosphorylates CDK1 to facilitate the G2/M transition (Wikipedia). CDC25A is frequently overexpressed in a wide range of human malignancies, including breast, lung, and nasopharyngeal cancers, where it acts as an oncogene that drives uncontrolled cell proliferation (Atlas of Genetics and Cytogenetics in Oncology and Haematology). Its overexpression is often associated with poor clinical prognosis, high-grade tumors, and resistance to chemotherapy (NIH PMC10108614). Beyond its role in cancer, aberrant activation of CDC25A has been linked to neurodegeneration in Alzheimer's and Parkinson's diseases (NIH PMC10108614). Therapeutic interventions targeting CDC25A include small-molecule inhibitors like NSC 663284 and BN82002, as well as RNA-based strategies such as antisense oligonucleotides and siRNAs designed to degrade CDC25A mRNA and inhibit protein synthesis (NIH PMC10108614; NIH PMC2583276). However, the clinical development of these agents is challenged by the essential role of CDC25A in normal cell division, which raises concerns regarding systemic toxicity in proliferative tissues and potential embryonic lethality (UniProt P30304; NIH PMC2583276).

Other names

M-phase inducer phosphatase 1Dual specificity phosphatase CDC25ACDC25A2Cell division cycle 25 homolog A

Inhibition of the dual-specificity phosphatase activity of CDC25A to prevent the dephosphorylation and activation of cyclin-dependent kinases (CDKs), or the use of RNA-targeting modalities like antisense oligonucleotides and siRNA to degrade CDC25A mRNA and reduce protein expression, leading to cell cycle arrest.