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

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 G alpha(13) signal destabilizes AhR by promoting the ubiquitination of AhR. G alpha(13) 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 G alpha(13) signal shows a potent inhibitory effect on the ligand-induced transcriptional activation of AhR. G alpha(13) results in the nuclear translocation of AhR in a ligand-independent manner. However, in the presence of active G alpha(13), AhR fails to form the active transcriptional complex. Taken together, we propose a new negative regulation of dioxin signalling by the G protein.