Discovery of Cancer-specific E3 Ligands for Targeted Protein Degradation
Time: 4:15 pm
day: Day 2 PM
Details:
- FBXW7 ubiquitinates and degrades many oncogenes such as cyclin E, c-JUN, c-MYC, NOTCH-1, and MCL-1 etc.; its hotspot mutation R465C loses substrate recognition, and drives cancer transformation through up-regulation of oncogene substrates
- Binding specifically to FBXW7 R465C mutant have been discovered through high throughput screening and validated by X-ray crystallography
- Degrading various protein targets in R465C mutant cell lines using PROTACs but not the wild-type cell lines, potentially representing a novel therapeutic approach against FBXW7 R465C mutant cancer