ERK inhibits Capicua repressor function via multisite phosphorylation - PubMed
2 hours ago
- #Capicua
- #Phosphorylation
- #ERK signaling
- ERK inhibits Capicua (Cic) repressor function through multisite phosphorylation.
- Capicua is a key target for ERK-mediated downregulation in Drosophila and mammals.
- Mutations in human CIC are linked to cancer and neurological diseases.
- Phosphorylation by ERK is critical for Cic downregulation, but specific sites in Drosophila Cic were previously unknown.
- The study identifies and validates ERK-targeted phosphorylation sites in Cic, distributed throughout the protein.
- A Cic mutant with 20 high-confidence phosphosites is resistant to degradation and acts as a 'super-repressor'.
- No single phosphorylation site is sufficient to inactivate Cic; multiple sites must be phosphorylated simultaneously for full downregulation.
- Multisite phosphorylation likely involves phosphodegrons recognized by ubiquitin ligases like Ago/FBXW7, leading to Cic degradation.
- The findings enhance understanding of signal interpretation in the RTK/ERK signaling network.