CBP/p300 functions as a possible transcriptional coactivator of Ah receptor nuclear translocator (Arnt)

Abstract

A heterodimer of AhR (aryl hydrocarbon receptor) and Arnt (AhR nuclear translocator) conveys a transactivation signal of aromatic hydrocarbons such as 2,3,7,8-tetrachlorodibenzo-p-dioxin and 3-methylcholanthrene to the genes for a group of drug-metabolizing enzymes. This inducible expression of the genes is inhibited by adenovirus E1A, suggesting that CBP/p300 is somehow involved in the transactivation of the genes by the AhR and Arnt heterodimer. Yeast and mammalian two hybrid systems revealed that CBP/p300 interacted with the transactivation domain of Arnt, but not with that of AhR, via the CREB-binding domain. The pull down assay using GST-Arnt hybrid protein confirmed the interaction between Arnt and CBP/p300. Considering these results and that Arnt or Arnt2 functions as a common partner in the formation of transcriptional regulators with other bHLH/PAS proteins such as AhR, HLF, and HIF-1alpha, the possibility arises that CBP/p300 is extensively involved as a coactivator in the transactivation process by bHLH/PAS (a conserved sequence motif among Per, Arnt, and Sim) heterodimer transcription factors through interaction with Arnt or Arnt2.