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 Galpha13 signal destabilizes AhR by promoting the ubiquitination of AhR. Galpha13 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 Galpha13 signal shows a potent inhibitory effect on the ligand-induced transcriptional activation of AhR. Galpha13 results in the nuclear translocation of AhR in a ligand-independent manner. However, in the presence of active Galpha13, AhR fails to form the active transcriptional complex. Taken together, we propose a new negative regulation of dioxin signalling by the G protein.
Nakata
Asuka
A
Department of Cell Biology, Graduate School of Biological Sciences, Nara Institute of Science and Technology, 8916-5 Takayama, Ikoma, Nara 630-0192, Japan.
Urano
Daisuke
D
Fujii-Kuriyama
Yoshiaki
Y
Mizuno
Norikazu
N
Tago
Kenji
K
Itoh
Hiroshi
H
D000818:Animals; D002460:Cell Line; D044365:GTP-Binding Protein alpha Subunits, G12-G13 / Q000378:metabolism*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D051379:Mice; D011485:Protein Binding; D011499:Protein Processing, Post-Translational; D055550:Protein Stability; D021381:Protein Transport; D018336:Receptors, Aryl Hydrocarbon / Q000378:metabolism*; D015398:Signal Transduction; D014158:Transcription, Genetic; D054875:Ubiquitination
D047908:Intracellular Signaling Peptides and Proteins; D018336:Receptors, Aryl Hydrocarbon; C103265:aryl hydrocarbon receptor-interacting protein; D044365:GTP-Binding Protein alpha Subunits, G12-G13