Rapid and Reversible Knockdown of Endogenously Tagged Endosomal Proteins via an Optimized HaloPROTAC Degrader.
Journal
ACS chemical biology
ISSN: 1554-8937
Titre abrégé: ACS Chem Biol
Pays: United States
ID NLM: 101282906
Informations de publication
Date de publication:
17 05 2019
17 05 2019
Historique:
pubmed:
13
4
2019
medline:
7
1
2020
entrez:
13
4
2019
Statut:
ppublish
Résumé
Inducing post-translational protein knockdown is an important approach to probe biology and validate drug targets. An efficient strategy to achieve this involves expression of a protein of interest fused to an exogenous tag, allowing tag-directed chemical degraders to mediate protein ubiquitylation and proteasomal degradation. Here, we combine improved HaloPROTAC degrader probes with CRISPR/Cas9 genome editing technology to trigger rapid degradation of endogenous target proteins. Our optimized probe, HaloPROTAC-E, a chloroalkane conjugate of high-affinity VHL binder VH298, induced reversible degradation of two endosomally localized proteins, SGK3 and VPS34, with a DC
Identifiants
pubmed: 30978004
doi: 10.1021/acschembio.8b01016
pmc: PMC6528276
doi:
Substances chimiques
Proteins
0
Class III Phosphatidylinositol 3-Kinases
EC 2.7.1.137
Protein Serine-Threonine Kinases
EC 2.7.11.1
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
882-892Subventions
Organisme : Medical Research Council
ID : MC_U127015387
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_UU_00018/1
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_UU_12016/2
Pays : United Kingdom
Organisme : Biotechnology and Biological Sciences Research Council
Pays : United Kingdom
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