Cloning of a Factor Required for Activity of the Ah (Dioxin) Receptor

Abstract

The aryl hydrocarbon (Ah) receptor binds various environmental pollutants, such as polycyclic aromatic hydrocarbons, heterocyclic amines, and polychlorinated aromatic compounds (dioxins, dibenzofurans, and biphenyls), and mediates the carcinogenic effects of these agents. The complementary DNA and part of the gene for an 87-kilodalton human protein that is necessary for Ah receptor function have been cloned. The protein is not the ligand-binding subunit of the receptor but is a factor that is required for the ligand-binding subunit to translocate from the cytosol to the nucleus after binding ligand. The requirement for this factor distinguishes the Ah receptor from the glucocorticoid receptor, to which the Ah receptor has been presumed to be similar. Two portions of the 87-kilodalton protein share sequence similarities with two Drosophila proteins, Per and Sim. Another segment of the protein shows conformity to the consensus sequence for the basic helix-loop-helix motif found in proteins that bind DNA as homodimers or heterodimers.

Functional analyses of the TEL-ARNT fusion protein underscores a role for oxygen tension in hematopoietic cellular differentiation

“…Plasmid, nucleic acids and protein methods Several plasmids used in our assays were kindly provided by the investigators: pVEGF-Luc and HIF1a (GL Semenza); ARNT (O Hankinson; Hoffman et al, 1991). TEL, Gal 4 and UAS-reporter vectors have been described previously Lopez et al, 1999).…”

“…The hypoxia inducible factor 1 (HIF1) is a major player in the cellular transcriptional response to hypoxia, leading to both local and systemic responses. Hypoxia inducible factor 1 is a dimeric factor composed from HIF1a and aryl hydrocarbon receptor nuclear translocator (ARNT1) subunit (Hoffman et al, 1991;Wang et al, 1995). They belong to a subclass of the basic region helix-loop-helix (bHLH) transcription factor family sharing Per, ARNT, Sim (PAS) domains.…”

The Aryl Hydrocarbon Receptor Complex and the Control of Gene Expression

“…For instance, it contained a bHLH region followed by two 51-amino acid Per-ARNTSim (PAS) A-B repeats 60 and an N-terminal glutamine-rich region. 58,65 The similarities between the AhR and ARNT, the presence of a bHLH, and previous observations on their interaction with enhancer DNA regions at the CYP1A1 promoter led to the hypothesis that the AhR and ARNT could be heterodimeric partners. In addition, the covalent binding of the photoaffinity ligand to the A-B region suggested that this region could be structurally part of a ligand-binding pocket that serves as a switch for the transformation of the AhR into a DNAbinding conformation.…”

Hypoxia-Inducible Factors and Kidney Vascular Development

“…This HRE was then used in DNA chromatography to purify HIF-1, which was shown to consist of two subunits, HIF-1␣ and HIF-1␤ (10). This was the first description of HIF-1␣, whereas HIF-1␤ was found to be identical to the aryl hydrocarbon receptor nuclear transporter (ARNT), which is a dimerization partner for the aryl hydrocarbon receptor (11). Two other bHLH-PAS members that dimerize with HIF-1␤ and share high sequence homology with HIF-1␣ have since been identified and named HIF-2␣ and HIF-3␣ (12,13).…”