Keystone Symposium: Targeted Protein Degradation: From Small Molecules to Complex Organelles

Targeted protein degradation is essential for the regulation of virtually all cellular functions. Perturbation of protein degradation pathways is associated with severe pathological conditions such as cancer, neurodegeneration and ageing disorders. This has fueled interest in obtaining fundamental insights into protein clearance pathways and to harness them for therapeutic applications. The major protein degradation pathways defined so far, the ubiquitin-proteasome system and autophagy, are usually discussed in separate conferences. However, it is now clear they are closely interconnected, raising the urgent need to discuss their interplay at the molecular and cellular levels. The meeting will bring together researchers from these different fields, who don’t normally meet at conferences, to build an encompassing and integrated vision of protein degradation. Topics to be discussed are: - Substrate recognition and processing by energy-dependent proteases as well as autophagy and lysosomal pathways. - Signals targeting proteins to distinct degradation pathways. - Interplay between proteolytic systems and chaperone pathways. - Reprogramming degradation with small molecules for therapeutic applications. - Degradation programs driving global proteome remodeling. An integrative meeting highlighting the connections between the different branches of protein degradation research: the ubiquitin-proteasome system, autophagy and small molecule-mediated reprogramming of proteolysis does not yet exist. The proposed meeting would be the first of its kind and will have a clear transformative potential to these fields. The attendees do not regularly meet and the meeting will therefore foster a more holistic view on targeted protein degradation and will expose the attendees to novel methods, techniques and approaches.