BRET-based RAS biosensors that show a novel small molecule is an inhibitor of RAS-effector protein-protein interactions.
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ICR Authors
Authors
Bery, N
Cruz-Migoni, A
Bataille, CJ
Quevedo, CE
Tulmin, H
Miller, A
Russell, A
Phillips, SE
Carr, SB
Rabbitts, TH
Cruz-Migoni, A
Bataille, CJ
Quevedo, CE
Tulmin, H
Miller, A
Russell, A
Phillips, SE
Carr, SB
Rabbitts, TH
Document Type
Journal Article
Date
2018-07-10
Date Accepted
2018-06-16
Abstract
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.
Citation
eLife, 2018, 7
Source Title
Publisher
ELIFE SCIENCES PUBLICATIONS LTD
ISSN
2050-084X
eISSN
2050-084X
Collections
Research Team
Chromosomal Translocations and Intracellular Antibody Therapeutics