BRET-based RAS biosensors that show a novel small molecule is an inhibitor of RAS-effector protein-protein interactions.
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Date
2018-07-10ICR Author
Author
Bery, N
Cruz-Migoni, A
Bataille, CJ
Quevedo, CE
Tulmin, H
Miller, A
Russell, A
Phillips, SE
Carr, SB
Rabbitts, TH
Type
Journal Article
Metadata
Show full item recordAbstract
The RAS family of proteins is amongst the most highly mutated in human cancers and has so far eluded drug therapy. Currently, much effort is being made to discover mutant RAS inhibitors and in vitro screening for RAS-binding drugs must be followed by cell-based assays. Here, we have developed a robust set of bioluminescence resonance energy transfer (BRET)-based RAS biosensors that enable monitoring of RAS-effector interaction inhibition in living cells. These include KRAS, HRAS and NRAS and a variety of different mutations that mirror those found in human cancers with the major RAS effectors such as CRAF, PI3K and RALGDS. We highlighted the utility of these RAS biosensors by showing a RAS-binding compound is a potent pan-RAS-effector interactions inhibitor in cells. The RAS biosensors represent a useful tool to investigate and characterize the potency of anti-RAS inhibitors in cells and more generally any RAS protein-protein interaction (PPI) in cells.
Collections
Subject
Humans
Biosensing Techniques
Signal Transduction
Energy Transfer
Protein Binding
Mutation
Proto-Oncogene Proteins p21(ras)
Protein Interaction Domains and Motifs
Small Molecule Libraries
HEK293 Cells
Bioluminescence Resonance Energy Transfer Techniques
Research team
Chromosomal Translocations and Intracellular Antibody Therapeutics
Language
eng
Date accepted
2018-06-16
License start date
2018-07-10
Citation
eLife, 2018, 7
Publisher
ELIFE SCIENCES PUBLICATIONS LTD
Except where otherwise noted, this item's license is described
as
https://creativecommons.org/licenses/by/4.0
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