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Cleavage stimulation factor 77 kDa subunit (CSTF3) is a core component of the cleavage stimulation factor (CSTF) complex, which is essential for the polyadenylation and 3' end cleavage of pre-mRNAs during mRNA maturation. CSTF3 acts as a scaffold protein, bridging other CSTF subunits (CSTF1 and CSTF2) and helping orchestrate protein-protein interactions necessary for efficient formation and nuclear localization of the active polyadenylation complex. It specifically enhances the affinity and specificity of CSTF-64 (CSTF2) for GU-rich regions downstream of pre-mRNA cleavage sites, playing a central regulatory role in the selection of polyadenylation sites and the generation of alternative mRNA transcript isoforms. Dysregulation of CSTF3 expression, or its alternative splicing, has been implicated in cancer progression, chemoresistance (notably to platinum agents in ovarian cancer), and can influence global mRNA profiles including 3' UTR length and stability. CSTF3 itself is not classically "druggable," but its expression and function are potential biomarkers and mechanistic drivers of oncogenic phenotypes or drug resistance[1][2][4][5][6].
Not classical drug target; however, altered CSTF3 expression modulates platinum resistance in ovarian cancer by regulating alternative polyadenylation of lncRNA NEAT1 and activating oncogenic signaling pathways (PI3K/AKT/mTOR). Modifies transcript isoform abundance and mRNA stability through 3' UTR processing.
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