Target intelligence / Profile preview

Cleavage stimulation factor 77 kDa subunit (CSTF3)

Target
CSTF3
Molecular classification
Other (RNA-binding protein), Polyadenylation factor, Pre-mRNA 3'-end processing complex
01

Overview

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].

Other names
Cleavage stimulation factor subunit 3CstF-77CSTF-77Cleavage stimulation factor, 3' pre-RNA, subunit 3, 77kDaCF-1 77 kDa subunitCSTF 77 kDa subunit
02

Mechanism of action

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.

03

Biological functions

mRNA 3'-end cleavagemRNA polyadenylationRegulation of alternative polyadenylationScaffold for protein–protein interactions in cleavage/polyadenylation complexRegulation of nuclear localization and RNA target selection for mRNA maturation
04

Disease associations

Cancer (including ovarian cancer, colorectal cancer, triple-negative breast cancer, gastric cancer)Chemotherapy resistance (notably platinum-based in ovarian cancer)Potential biomarker in multiple oncological contextsOculopharyngeal muscular dystrophy 1 (reported association)
05

Safety considerations

No characterized safety concerns for therapeutic targeting, as CSTF3 is essential for mRNA processing and global cell function; theoretical risk of toxicity if systemically inhibited due to ubiquitous role in gene expressionNo drugs selectively antagonizing CSTF3 currently in clinical use or trials
06

Interacting drugs

Platinum compounds (as context for resistance, not as classic molecular inhibitors or binders)

2 more in the full profile.

07

Biomarkers

CSTF3 expression (level or splicing variant) as a biomarker for platinum resistance in ovarian cancer and as a prognostic indicator in colorectal and gastric cancerNEAT1_1 isoform (product of CSTF3-regulated alternative polyadenylation) in ovarian cancer

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