Format

Send to

Choose Destination
Trends Biochem Sci. 2019 Jan;44(1):75-89. doi: 10.1016/j.tibs.2018.09.014. Epub 2018 Oct 13.

Proteomics and Beyond: Cell Decision-Making Shaped by Reactive Electrophiles.

Author information

1
École Polytechnique Fédérale de Lausanne, Institute of Chemical Sciences and Engineering, 1015, Lausanne, Switzerland; Department of Chemistry and Chemical Biology, Cornell University, Ithaca, NY 14853, USA; Equal contributors.
2
Department of Chemistry and Chemical Biology, Cornell University, Ithaca, NY 14853, USA; Equal contributors.
3
École Polytechnique Fédérale de Lausanne, Institute of Chemical Sciences and Engineering, 1015, Lausanne, Switzerland. Electronic address: yimon.aye@epfl.ch.

Abstract

Revolutionary proteomic strategies have enabled rapid profiling of the cellular targets of electrophilic small molecules. However, precise means to directly interrogate how these individual electrophilic modifications at low occupancy functionally reshape signaling networks have until recently been largely limited. We highlight here new methods that transcend proteomic platforms to forge a quantitative link between protein target-selective engagement and downstream signaling. We focus on recent progress in the study of non-enzyme-assisted signaling mechanisms and crosstalk choreographed by native reactive electrophilic species (RES). Using this as a model, we offer a long-term vision of how these toolsets together with fundamental biochemical knowledge of precision electrophile signaling may be harnessed to assist covalent ligand-target matching and ultimately amend disease-specific signaling dysfunction.

PMID:
30327250
DOI:
10.1016/j.tibs.2018.09.014

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center