Constructing de novo H2O2 signaling via induced protein proximity

A new chemical strategy has been developed to generate de novo signaling pathways that link a signaling molecule, H2O2, to different downstream cellular events in mammalian cells. This approach combines the reactivity-based H2O2 sensing with the chemically induced protein proximity technology. By chemically modifying abscisic acid with an H2O2-sensitive boronate ester probe, novel H2O2 signaling pathways can be engineered to induce transcription, protein translocation and membrane ruffle formation upon exogenous or endogenous H2O2 stimulation. This strategy has also been successfully applied to gibberellic acid, which provides the potential to build signaling networks based on orthogonal cell stimuli.