G-protein signalling negatively regulates the stability of aryl hydrocarbon receptor

Abstract

Aryl hydrocarbon receptor (AhR) is a transcription factor that works as a dioxin receptor and is also involved in various physiological phenomena, including development and cell proliferation. Here, we show that the Gα13 signal destabilizes AhR by promoting the ubiquitination of AhR. Gα13 interacts directly with AhR-interacting protein (AIP) and inhibits the interaction between AhR and AIP, a crucial interacting protein of AhR. Strikingly, a reporter gene assay and a quantitative reverse transcription-PCR analysis indicate that the Gα13 signal shows a potent inhibitory effect on the ligand-induced transcriptional activation of AhR. Gα13 results in the nuclear translocation of AhR in a ligand-independent manner. However, in the presence of active Gα13, AhR fails to form the active transcriptional complex. Taken together, we propose a new negative regulation of dioxin signalling by the G protein.