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.