A salicylic acid-inducible gene expression system for mammalian cells
Ligand inducible proteins that enable precise and reversible control of nuclear translocation ofpassenger proteins have broad applications ranging from genetic studies in mammals to therapeutics that target diseases such as cancer and diabetes. One of the drawbacks of the current translocation systems is that the ligands used to control nuclear localization are either toxic or prone to crosstalk with endogenous protein cascades within live animals. We sought to take advantage of salicylic acid (SA), a small molecule that has been extensively used in humans. In plants, SA functions as a hormone that can mediate immunity and is sensed by the non-expressor of pathogenesis-related (NPR) proteins. Although it is well recognized that nuclear translocation of NPR1 is essential to promoting immunity in plants, the exact subdomain of Arabidopsis thaliana NPR1 (AtNPR1) essential for SA mediated nuclear translocation is controversial. We show that the TAD of AtNPR1 is sufficient to enable the reversible SA mediated nuclear translocation of mCherry in human cells. Our studies advance a basic understanding of nuclear translocation mediated by the TAD of AtNPR1 and uncover a biotechnological tool for SA mediated nuclear localization.

63/254,862, (Provisional, Pre-Conversion)

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Navin Varadarajan
Professor, Chemical Engineering