Preprint Review Version 1 Preserved in Portico This version is not peer-reviewed

Keap 1: The New Janus Word on the Block

Version 1 : Received: 9 April 2022 / Approved: 11 April 2022 / Online: 11 April 2022 (10:39:31 CEST)

How to cite: Marcus, L.; Aye, Y. Keap 1: The New Janus Word on the Block. Preprints 2022, 2022040093. Marcus, L.; Aye, Y. Keap 1: The New Janus Word on the Block. Preprints 2022, 2022040093.


Here we draw insights from the latest serendipitous findings made on the opposing roles of a validated drug-target protein Keap1. We weigh up how natural reactive electrophiles and electrophilic small-molecule drugs in clinical use directly impinge on seemingly conflicting, yet both Keap1-electrophile-modification-dependent, cell-survival- vs. cell-death-promoting behaviors. In the process, we convey how understanding reactive chemical-signal regulation at a single-protein-specific level is an enabling necessity in deconstructing otherwise intricate reactive-small-molecule-responsive cellular pathways. We hope this opinion piece further spurs the broader interests of basic and pharmaceutical research communities toward better understanding of molecular mechanisms underpinning reactive small-molecule-regulated signaling subsystems.


Electrophile signaling; drug mechanism; immunology; antioxidant response; apoptosis


Biology and Life Sciences, Immunology and Microbiology

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