The Die Is Cast: Precision Electrophilic Modifications Contribute to Cellular Decision Making.
This perspective sets out to critically evaluate the scope of reactive electrophilic small molecules as unique chemical signal carriers in biological information transfer cascades. We consider these electrophilic cues as a new volatile cellular currency and compare them to canonical signaling circulation such as phosphate in terms of chemical properties, biological specificity, sufficiency, and necessity. The fact that nonenzymatic redox sensing properties are found in proteins undertaking varied cellular tasks suggests that electrophile signaling is a moonlighting phenomenon manifested within a privileged set of sensor proteins. The latest interrogations into these on-target electrophilic responses set forth a new horizon in the molecular mechanism of redox signal propagation wherein direct low-occupancy electrophilic modifications on a single sensor target are biologically sufficient to drive functional redox responses with precision timing. We detail how the various mechanisms through which redox signals function could contribute to their interesting phenotypic responses, including hormesis.
Department of Chemistry & Chemical Biology, Cornell University , 244 Baker Laboratory, Ithaca, New York 14850, United States.
Marcus J C
MJC
Long
Department of Chemistry & Chemical Biology, Cornell University , 244 Baker Laboratory, Ithaca, New York 14850, United States.|Department of Biochemistry, Weill Cornell Medicine , 1300 York Avenue, New York, New York 10065, United States.
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