Figure 1.

Intersecting canonical signaling with redox signaling. (Left). Canonical signaling paradigms are defined by enzyme-mediated installation/ removal of covalent modifications such as phosphate (P) or ubiquitin (Ub). (Right). Redox-linked signaling pathways—especially those regulated by reactive electrophilic species (RES)—defy these paradigms because no enzyme mediation occurs at the point of signal adduction to target proteins. ROS modifications are further differentiated by the established disulfide/thiol-sulfenic-acid-based signal relay mechanisms as well as enzyme-assisted reversal of certain ROS modifications. By contrast, RES modifications are largely irreversible. Importantly, redox-linked chemical messages often cross-talk with canonical messages in propagating biological signals.