Related Experiment Video
Updated: Aug 5, 2025

High-Throughput Cellular Profiling of Targeted Protein Degradation Compounds Using HiBiT CRISPR Cell Lines
Published on: November 9, 2020
The application of targeted protein degradation technologies to G protein-coupled receptors
Alastair C Keen1, Manuela Jörg2,3, Michelle L Halls1
1Drug Discovery Biology Theme, Monash Institute of Pharmaceutical Sciences, Monash University, 399 Royal Parade, Parkville, 3052, Victoria, Australia.
Abstract:
The ubiquitin-proteasome system is one of the major pathways for the degradation of cellular proteins. In recent years, methods have been developed to exploit the ubiquitin-proteasome system to artificially degrade target proteins. Targeted protein degraders are extremely useful as biological tools for discovery research. They have also been developed as novel therapeutics with several targeted protein degraders currently in clinical trials. However, almost all targeted protein degrader technologies have been developed for cytosolic proteins. The G protein-coupled receptor (GPCR) superfamily is one of the most important classes of drug targets, yet only limited examples of GPCR degradation exist. Here, we review these examples and provide a perspective on the different strategies that have been used to apply targeted protein degradation to GPCRs. We also discuss whether alternative approaches that have been used to degrade other integral membrane proteins could be applied to the degradation of GPCRs. LINKED ARTICLES: This article is part of a themed issue Therapeutic Targeting of G Protein-Coupled Receptors: hot topics from the Australasian Society of Clinical and Experimental Pharmacologists and Toxicologists 2021 Virtual Annual Scientific Meeting. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v181.14/issuetoc.
Related Concept Videos
GPCR Desensitization
G Protein-coupled Receptors
GPCRs are also called heptahelical, 7TM, or serpentine receptors, and consist of seven (H1-H7) transmembrane alpha-helices that span the bilayer to form a cylindrical core. The transmembrane helices are connected by three extracellular loops and three...
Regulated Protein Degradation
Protein degradation plays two important roles in the cells. It helps to protect cells from misfolded or damaged proteins before they lead to a...
Amplifying Signals via Enzymatic Cascade
Transducer Mechanism: G Protein–Coupled Receptors
GPCRs are also called heptahelical,...
G-protein Coupled Receptors

