This project deals with the discovery of an appropriate chemical tool that allows the study of a protein. This protein is called ubiquitin-specific protease 2 (USP2) and belongs the superfamily of deubiquitinating enzymes (DUBs). While USP2 has been associated with a wide variety of cancers and represents a very promising therapeutic target, it still requires to be validated for its therapeutic potential. In that context, having an appropriate chemical tool would allow a confident interrogation and further understanding of USP2 biology and disease. This tool can likewise serve as starting point and eventually feed drug discovery projects for USP2-targeted treatments. To this end, an innovative approach endowed with great potential has recently emerge. This technology is called proteolysis-targeting chimera (PROTAC) and consists of pursuing the degradation of a protein that is upregulated, thereby evoking a certain disease. Herein, we aimed at the development of an USP2-targeted degrader (USP2-TD) based on PROTAC technology. This research has been carried out in the Spring group at the University of Cambridge and involved a 6-month placement in the Ciulli group at the University of Dundee.
At the time of the end of the action, the project is still ongoing. Preliminary data showed two major findings:
- We identified a candidate with the potential to become an USP2-TD.
- We discovered a natural interaction between USP2 and an unrelated complex of proteins.
Given these promising results, these projects will be investigated in a collaboration between the Universities of Barcelona, Cambridge, and Dundee. Success in these studies can lead to major advances in the knowledge and treatment of USP2-related diseases.
