To proteomics and beyond: Cell decision making shaped by reactive electrophiles
Trends in Biochemical Sciences (Elsevier) — just accepted (September 2018)
Revolutionary proteomics 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. Here we highlight new methods that transcend proteomics 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 electrophiles. Using this as a model, we offer a long-term vision on how these toolsets along with the fundamental biochemical knowledge of precision electrophile signaling may be harnessed to assist covalent ligand–target matching and ultimately amend a disease-specific signaling dysfunction..
Xuyu Liu#, Marcus J. C. Long#, and Yimon Aye*
(#, co-first authors. *, corresponding author)