| Autor: |
Merve Mutlu, Isabel Schmidt, Andrew I. Morrison, Benedikt Goretzki, Felix Freuler, Damien Begue, Oliver Simic, Nicolas Pythoud, Erik Ahrne, Sandra Kapps, Susan Roest, Debora Bonenfant, Delphine Jeanpierre, Thi-Thanh-Thao Tran, Rob Maher, Shaojian An, Amandine Rietsch, Florian Nigsch, Andreas Hofmann, John Reece-Hoyes, Christian N. Parker, Danilo Guerini |
| Jazyk: |
angličtina |
| Rok vydání: |
2024 |
| Předmět: |
|
| Zdroj: |
Nature Communications, Vol 15, Iss 1, Pp 1-16 (2024) |
| Druh dokumentu: |
article |
| ISSN: |
2041-1723 |
| DOI: |
10.1038/s41467-024-48922-w |
| Popis: |
Abstract Stimulator of interferon genes (STING) is a central component of the cytosolic nucleic acids sensing pathway and as such master regulator of the type I interferon response. Due to its critical role in physiology and its’ involvement in a variety of diseases, STING has been a focus for drug discovery. Targeted protein degradation (TPD) has emerged as a promising pharmacology for targeting previously considered undruggable proteins by hijacking the cellular ubiquitin proteasome system (UPS) with small molecules. Here, we identify AK59 as a STING degrader leveraging HERC4, a HECT-domain E3 ligase. Additionally, our data reveals that AK59 is effective on the common pathological STING mutations, suggesting a potential clinical application of this mechanism. Thus, these findings introduce HERC4 to the fields of TPD and of compound-induced degradation of STING, suggesting potential therapeutic applications. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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