Auxin Triggers AHR Pathway Activation in the Auxin-Inducible Degron System in Mammalian Cells

The auxin-inducible degron (AID) system is widely used to study function of various proteins. The plant hormone auxin is used as an inducer in this system, which easily penetrates into the cells and causes proteasomal degradation of the protein of interest fused to a small degron tag. It is often assumed that as a plant hormone, auxin does not significantly affect physiology of animal cells. In order to test how auxin affects gene expression in human and mouse cells, we collected a set of published data on the levels of gene expression in various experiments with the auxin degradation system of various proteins. The analysis showed that in human HCT116, DLD1, and HAP1 cell lines, as well as in mouse embryonic stem cell lines, auxin treatment leads to activation of aryl hydrocarbon receptor (AHR)-related genes. However, activation of AHR pathway genes does not occur upon auxin treatment in the human IMR32 cells and mouse G1E-ER4 cells, which are characterized by low AHR gene expression. To verify this observation, we conducted an experiment treating human U87, A549, and HCT116 cells with auxin and demonstrated activation of one of the main AHR pathway responders, the CYP1B1 gene. We believe that activation of the AHR pathway should be taken into account by those using the auxin degradation system in their studies.