Commentary: Localization matters!
- Kerstin Koch
- Oct 20, 2022
- 1 min read
Updated: May 22, 2024
In the latest issue of Cell Chemical Biology, PROXIDRUGS scientists Varun Shah and Ivan Đikić comment on an article published by Simpson et al from MRC's Protein Phosphorylation & Ubiquitiylation Unit at University Dundee. The work of Simpson and colleagues shows that accessibility of the target protein by PROTAC-
mediated degradation varies depending on subcellular localization of the target. The commentary points out that it would be highly interesting to learn more about diffusibility of PROTACs within cells – one of the many challenges in the field that need to be explored yet.
Engaging organelle-specific E3s to degrade a specific targets may even help to reduce off-target effects. As Shah and Đikić summarize, this work once more raises the question as to what extent the global proteome can be targeted with just a small selection of E3 ligases bein available yet. Surely the exploiting of additional E3 ligases, that show tissue-specific expression or context-dependent regulation could significantly expand the therapeutic application space of PROTACs.
