Ubiquitin conjugation is central to any cellular process in eukaryotes, but its intricacies have made it hard to resolve. The necessity of cascades of conjugating enzymes (E1/E2/E3), the variety of chain types, the low affinity of its components, the avidity between different ubiquitin type signals have all combined to make this process hard to study. There are roles for ubiquitin-dependent regulation in many different diseases, particularly in cancer, developmental disease and neurological disorders such as Huntington’s disease and Parkinson.
In drug discovery, the realization that ubiquitin modification can lead to degradation by the proteasome has been crucial for the development of a new type of therapeutic modality, the so-called degraders such as PROTACS and molecular glues, that bring the ubiquitin conjugation machinery to a desired target and induce its degradation. Such drugs have very different pharmacokinetic profiles than previous modalities and can target otherwise undruggable proteins. This year, the first of these PROTACs have been approved by the FDA, proving the importance of this approach for drug discovery.
Here we want to bring together researchers involved in different aspects of ubiquitin and ubiquitin-like regulation and degrader development, in order to promote the research and maximize interaction in the Netherlands. We will give special attention to degrader development, with a keynote lecture from Stefan Knapp (SGC/Goethe University Frankfurt).
