O-GlcNAcylation stabilizes RSK4 by antagonizing GSK3β-mediated phosphorylation to enhance radioresistance in esophageal squamous cell carcinoma - PubMed
4 days ago
- #RSK4
- #O-GlcNAcylation
- #radioresistance
- O-GlcNAcylation stabilizes RSK4 by inhibiting GSK3β-mediated phosphorylation, enhancing radioresistance in esophageal squamous cell carcinoma (ESCC).
- RSK4 stability and activity are regulated by phosphorylation (Thr402/Ser406 by GSK3β) and O-GlcNAcylation (Thr405 by OGT), which antagonize each other.
- O-GlcNAcylation of RSK4 prevents its degradation via the FBXW7-dependent proteasomal pathway, promoting cancer stem cell (CSC) properties and radioresistance.
- Targeting RSK4 O-GlcNAcylation with OSMI-4 destabilizes RSK4 and sensitizes ESCC to radiotherapy in preclinical models.
- This study identifies RSK4 O-GlcNAcylation as a potential therapeutic target to improve radiotherapy efficacy in ESCC.