Date

Tuesday 20 Jan 2026

Time

15:15 - 15:45

Location

BW029

Supervisor

Zach Armstrong

Jury

Marta Artola Perez de Azanza

Targeted Protein Degradation (TPD) is an emerging field in the last few years and has the potential to drug disease causing proteins which were previously thought to be undruggable, such as transcription factors (TFs). The concept of Proteolysis Targeting Chimera (PROTAC) is more than 20 years old and a handful of PROTACs are currently in clinical trails. PROTACs, which are bifunctional molecules, rely on hijacking the cells own degradation system by targeting an E3 ubiquitin ligase. The majority of existing PROTACs function by recruiting the CRBN (Cereblon) or VHL (Von Hippel-Lindau) E3 ligase. However, these E3 ligases have their limitations, for example, these E3 ligases have non specified (subcellular) localisation. This poses a significant limitation as it prevents spatially controlled activity, and thereby increasing the risk for off target toxicity. To effectively target nuclear restricted proteins, such as TFs, a logical optimization would be to develop PROTACs targeting E3 ligase and Protein of Interests (POI) which are better matched in terms of (sub)cellular localisation. In recent years, many studies have strived to increase the toolbox of potential E3 ubiquitin ligases that can be recruited by identifying new ligandable E3 ubiquitin ligases. This review will focus on recent improvements made in the recruitment of nuclear restricted E3 ubiquitin ligases for the purpose of PROTACs.