A novel chemical strategy has been developed to generated de novo signaling pathways that integrates the chemically induced proximity (CIP) technology and the reactivity-based signal sensing to control tailored cellular events in mammalian cells. This approach enables cells to link H2O2 or Fe2+ with different cellular responses including gene activation, protein translocation and cytoskeleton remodeling. This method uses caged CIP inducers (e.g. abscisic acid (ABA), gibberellin acid (GA)) that are inactive until being stimulated by a specific signal (e.g. H2O2 or Fe2+) which removes the caging group and activates an inducer to promote the dimerization of the adapter protein pairs (e.g. ABI&PYL, GAI&GID1). This technology was utilized to design signal circuitry incorporating “AND” and “OR” biologic gates that enables mammalian cells to translate different combinations of Fe2+ and H2O2 signals into pre-defined biological output.

Constructing de novo small molecules responses via signal-induced protein proximity in mammalian cells: Chemically engineer cell behaviors & signaling

253rd National Meeting (2017)

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