Scientific article

Luciferase Controlled Protein Interactions

Published inJournal of the American Chemical Societ, vol. 143, no. 10, p. 3665-3670
Publication date2021

Protein trafficking and protein–protein interactions (PPIs) are central to regulatory processes in cells. Induced dimerization systems have been developed to control PPIs and regulate protein trafficking (localization) or interactions. Chemically induced dimerization (CID) has proven to be a robust approach to control protein interactions and localization. The most recent embodiment of this technology relies on CID conjugates that react with a self-labeling protein on one side and a photocaged ligand on the other side to provide spatiotemporal control of the interaction with the protein of interest. Advancing this technology further is limited by the light delivery problem and the phototoxicity of intense irradiation necessary to achieve photouncaging. Herein, we designed a novel chemically induced dimerization system that was triggered by bioluminescence, instead of external light. Protein dimerization showed fast kinetics and was validated by an induced change of localization of a target protein (to and from the nucleus or plasma membrane) upon trigger. The technology was used transiently to activate the phosphatidylinositol 3-kinase (PI3K)/mTOR pathway and measure the impact on lipid synthesis/metabolism, assessed by lipidomics.

  • Swiss National Science Foundation - 185898
Citation (ISO format)
CHANG, Dalu et al. Luciferase Controlled Protein Interactions. In: Journal of the American Chemical Societ, 2021, vol. 143, n° 10, p. 3665–3670. doi: 10.1021/jacs.0c11016
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