دورية أكاديمية
Target protein localization and its impact on PROTAC-mediated degradation
| العنوان: | Target protein localization and its impact on PROTAC-mediated degradation |
|---|---|
| المؤلفون: | Simpson, Luke M., Glennie, Lorraine, Brewer, Abigail, Zhao, Jin-Feng, Crooks, Jennifer, Shpiro, Natalia, Sapkota, Gopal P. |
| المصدر: | Simpson , L M , Glennie , L , Brewer , A , Zhao , J-F , Crooks , J , Shpiro , N & Sapkota , G P 2022 , ' Target protein localization and its impact on PROTAC-mediated degradation ' , Cell Chemical Biology , vol. 29 , no. 10 , pp. 1482-1504.e7 . https://doi.org/10.1016/j.chembiol.2022.08.004Test |
| سنة النشر: | 2022 |
| المجموعة: | Discovery - University of Dundee Online Publications |
| مصطلحات موضوعية: | proteolysis-targeting chimera (PROTAC), Targeted protein degradation (TPD), protein localization, degrader, dTAG, Halo, VHL, cereblon, CRBN, E3, HiBiT, /dk/atira/pure/subjectarea/asjc/3000/3002, name=Drug Discovery, /dk/atira/pure/subjectarea/asjc/1300/1313, name=Molecular Medicine, /dk/atira/pure/subjectarea/asjc/1300/1312, name=Molecular Biology, /dk/atira/pure/subjectarea/asjc/1300/1303, name=Biochemistry, /dk/atira/pure/subjectarea/asjc/1300/1308, name=Clinical Biochemistry, /dk/atira/pure/subjectarea/asjc/3000/3004, name=Pharmacology |
| الوصف: | Proteolysis-targeting chimeras (PROTACs) bring a protein of interest (POI) into spatial proximity of an E3 ubiquitin ligase, promoting POI ubiquitylation and proteasomal degradation. PROTACs rely on endogenous cellular machinery to mediate POI degradation, therefore the subcellular location of the POI and access to the E3 ligase being recruited potentially impacts PROTAC efficacy. To interrogate whether the subcellular context of the POI influences PROTAC-mediated degradation, we expressed either Halo or FKBP12F36V (dTAG) constructs consisting of varying localization signals and tested the efficacy of their degradation by von Hippel-Lindau (VHL)- or cereblon (CRBN)-recruiting PROTACs targeting either Halo or dTAG. POIs were localized to the nucleus, cytoplasm, outer mitochondrial membrane, endoplasmic reticulum, Golgi, peroxisome or lysosome. Differentially localized Halo or FKBP12F36V proteins displayed varying levels of degradation using the same respective PROTACs, suggesting therefore that the subcellular context of the POI can influence the efficacy of PROTAC-mediated POI degradation. |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | application/pdf |
| اللغة: | English |
| العلاقة: | https://discovery.dundee.ac.uk/en/publications/1b78f0bd-7662-418b-a4d9-33149454ca2aTest |
| DOI: | 10.1016/j.chembiol.2022.08.004 |
| الإتاحة: | https://doi.org/10.1016/j.chembiol.2022.08.004Test https://discovery.dundee.ac.uk/en/publications/1b78f0bd-7662-418b-a4d9-33149454ca2aTest https://discovery.dundee.ac.uk/ws/files/80555670/PIIS2451945622003129.pdfTest http://www.scopus.com/inward/record.url?scp=85140068494&partnerID=8YFLogxKTest |
| حقوق: | info:eu-repo/semantics/openAccess |
| رقم الانضمام: | edsbas.539C8D15 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1016/j.chembiol.2022.08.004 |
|---|