Target type: cellularcomponent
An aryl hydrocarbon receptor (AhR) complex found in the nucleus; ; consists of ligand-bound AhR and the aryl hydrocarbon receptor nuclear translocator (ARNT). [PMID:7598497]
The nuclear aryl hydrocarbon receptor (AhR) complex is a multi-protein assembly that plays a crucial role in mediating the cellular response to environmental toxins, particularly polycyclic aromatic hydrocarbons (PAHs) like benzo[a]pyrene. The complex resides within the nucleus and is composed of the following key components:
1. **AhR**: This is the ligand-binding component of the complex. It is a transcription factor that exists in the cytoplasm in an inactive state, bound to chaperone proteins like heat shock protein 90 (Hsp90) and AIP. Upon binding to its ligand, AhR undergoes a conformational change, releasing the chaperone proteins and translocating to the nucleus.
2. **ARNT (Aryl hydrocarbon Receptor Nuclear Translocator)**: This is a transcription factor that acts as the dimerization partner of AhR. It is constitutively localized in the nucleus and forms a heterodimer with the activated AhR.
3. **Other Co-regulatory Factors**: Several other proteins can interact with the AhR/ARNT complex and modulate its activity. These include:
* **X-associated protein 2 (XAP2)**: This protein acts as a co-chaperone for AhR in the cytoplasm, preventing its premature nuclear translocation.
* **Nuclear receptor coactivators (NCoRs)**: These proteins enhance the transcriptional activity of the complex by recruiting histone acetyltransferases (HATs) to the DNA.
* **Histone deacetylases (HDACs)**: These proteins can suppress the transcriptional activity of the complex by deacetylating histones.
* **Other DNA-binding proteins**: These proteins can interact with the AhR/ARNT complex and influence its binding to specific DNA sequences.
The AhR complex ultimately binds to specific DNA sequences known as "dioxin response elements" (DREs) located in the promoter regions of target genes. This binding leads to the recruitment of RNA polymerase and the initiation of transcription, ultimately influencing the expression of genes involved in detoxification, cell growth, differentiation, and immune response. Therefore, the nuclear AhR complex is a key player in regulating cellular responses to environmental insults and maintaining cellular homeostasis.'
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| Protein | Definition | Taxonomy |
|---|---|---|
| Aryl hydrocarbon receptor | An aryl hydrocarbon receptor that is encoded in the genome of human. [PRO:DNx, UniProtKB:P35869] | Homo sapiens (human) |
| Compound | Definition | Classes | Roles |
|---|---|---|---|
| dibenzofuran | dibenzofuran : A mancude organic heterotricyclic parent that consists of a furan ring flanked by two benzene rings ortho-fused across the 2,3- and 4,5-positions. dibenzofurans : Any organic heterotricyclic compound based on a dibenzofuran skeleton and its substituted derivatives thereof. Dibenzofurans: Compounds that include the structure of dibenzofuran. | dibenzofurans; mancude organic heterotricyclic parent; polycyclic heteroarene | xenobiotic |
| 3-methylcholanthrene | 3-methylcholanthrene : A pentacyclic ortho- and peri-fused polycyclic arene consisting of a dihydrocyclopenta[ij]tetraphene ring system with a methyl substituent at the 3-position. Methylcholanthrene: A carcinogen that is often used in experimental cancer studies. | ortho- and peri-fused polycyclic arene | aryl hydrocarbon receptor agonist; carcinogenic agent |
| 5,11-dihydroindolo[3,2-b]carbazole-12-carboxaldehyde | indolocarbazole | ||
| benzo(a)pyrene | Benzo(a)pyrene: A potent mutagen and carcinogen. It is a public health concern because of its possible effects on industrial workers, as an environmental pollutant, an as a component of tobacco smoke. benzo[a]pyrene : An ortho- and peri-fused polycyclic arene consisting of five fused benzene rings. | ortho- and peri-fused polycyclic arene | carcinogenic agent; mouse metabolite |
| beta-naphthoflavone | beta-naphthoflavone : An extended flavonoid resulting from the formal fusion of a benzene ring with the f side of flavone. beta-Naphthoflavone: A polyaromatic hydrocarbon inducer of P4501A1 and P4501A2 cytochromes. (Proc Soc Exp Biol Med 1994 Dec:207(3):302-308) | extended flavonoid; naphtho-gamma-pyrone; organic heterotricyclic compound | aryl hydrocarbon receptor agonist |
| bisacodyl | Bisacodyl: A diphenylmethane stimulant laxative used for the treatment of CONSTIPATION and for bowel evacuation. (From Martindale, The Extra Pharmacopoeia, 30th ed, p871) | diarylmethane | |
| kynurenic acid | kynurenic acid : A quinolinemonocarboxylic acid that is quinoline-2-carboxylic acid substituted by a hydroxy group at C-4. Kynurenic Acid: A broad-spectrum excitatory amino acid antagonist used as a research tool. | monohydroxyquinoline; quinolinemonocarboxylic acid | G-protein-coupled receptor agonist; human metabolite; neuroprotective agent; nicotinic antagonist; NMDA receptor antagonist; Saccharomyces cerevisiae metabolite |
| indigo | hydroxyindoles | ||
| 2,3,7,8-tetrachlorodibenzodioxine | Tetrachlorodibenzodioxin: A mixture of isomers. | polychlorinated dibenzodioxine | |
| 2,4,2',4'-tetrachlorobiphenyl | 2,2',4,4'-tetrachlorobiphenyl : A tetrachlorobiphenyl that is biphenyl in which each of the phenyl groups is substituted at positions 2 and 4 by chlorines. 2,4,2',4'-tetrachlorobiphenyl: structure | dichlorobenzene; tetrachlorobiphenyl | |
| octachlorodibenzo-4-dioxin | octachlorodibenzo-4-dioxin: RN given refers to unlabeled parent cpd | polychlorinated dibenzodioxine | |
| 2-chlorodibenzofuran | 2-chlorodibenzofuran: structure | ||
| 1,2,3,4-tetrachlorodibenzodioxin | 1,2,3,4-tetrachlorodibenzodioxin: structure given in first source | polychlorinated dibenzodioxine | |
| pcb 118 | dichlorobenzene; pentachlorobiphenyl; trichlorobenzene | ||
| 3,4,3',4'-tetrachlorobiphenyl | 3,3',4,4'-tetrachlorobiphenyl : A tetrachlorobiphenyl that is biphenyl in which the hydrogens at position 3 and 4 on each phenyl group are replaced by chlorines. 3,4,3',4'-tetrachlorobiphenyl: RN given refers to parent cpd | dichlorobenzene; tetrachlorobiphenyl | |
| 2,3,3',4,4'-pentachlorobiphenyl | dichlorobenzene; pentachlorobiphenyl; trichlorobenzene | ||
| 2,3,4,5-tetrachlorobiphenyl | tetrachlorobiphenyl : Any polychlorobiphenyl with molecular formula C12H6Cl4. | tetrachlorobenzene; tetrachlorobiphenyl | |
| 1,2,7,8-tetrachlorodibenzo-p-dioxin | 1,2,7,8-tetrachlorodibenzo-p-dioxin: structure in first source | ||
| 2,4,5,2',4',5'-hexachlorobiphenyl | hexachlorobiphenyl | ||
| 2,3,3',4,4',5-hexachlorobiphenyl | dichlorobenzene; hexachlorobiphenyl; tetrachlorobenzene | ||
| 2,8-dichlorodibenzo-4-dioxin | 2,8-dichlorodibenzo-4-dioxin: metabolite for 2,3,7,8-TCDD | ||
| 1,2,3,4,7,8-hexachlorodibenzodioxin | 1,2,3,4,7,8-hexachlorodibenzodioxin: structure given in first source | polychlorinated dibenzodioxine | |
| 1,2,4-trichlorodibenzo-1,4-dioxin | 1,2,4-trichlorodibenzo-1,4-dioxin: structure given in first source | ||
| 1,2,3,7,8-pentachlorodibenzo-p-dioxin | polychlorinated dibenzodioxine | ||
| 2,3,7,8-tetrabromodibenzo-4-dioxin | 2,3,7,8-tetrabromodibenzo-4-dioxin: structure given in first source 2,3,7,8-tetrabromodibenzodioxine : An organobromine compound that is dibenzodioxine carrying four bromo substituents at positions 2, 3, 7 and 8. | dibenzodioxine; organobromine compound | |
| 2,3,7,8-tetrachlorodibenzofuran | 2,3,7,8-tetrachlorodibenzofuran: toxic product which was generated in Italy due to an explosion in a plant manufacturing 2,4,5-trichlorophenol | polychlorinated dibenzofuran | |
| 2,3,4,7,8-pentachlorodibenzofuran | 2,3,4,7,8-pentachlorodibenzofuran: structure given in first source | polychlorinated dibenzofuran | |
| 1,2,3,7,8-pentachlorodibenzofuran | 1,2,3,7,8-pentachlorodibenzofuran: structure given in first source; RN given refers to parent cpd | polychlorinated dibenzofuran | |
| 1,2,3,4,7,8-hexachlorodibenzofuran | polychlorinated dibenzofuran | ||
| 2,3,4,4'5-pentachlorobiphenyl | monochlorobenzenes; pentachlorobiphenyl; tetrachlorobenzene | ||
| 3,4,5,3',4'-pentachlorobiphenyl | 3,3',4,4',5-pentachlorobiphenyl : A pentachlorobiphenyl in which the chlorines are located at the 3, 4, 5, 3', and 4' positions. | pentachlorobiphenyl; trichlorobenzene | |
| 6-methyl-1,3,8-trichlorodibenzofuran | 6-methyl-1,3,8-trichlorodibenzofuran: structure given in first source | ||
| kynurenine | L-kynurenine : A kynurenine that has L configuration. | amino acid zwitterion; kynurenine; non-proteinogenic L-alpha-amino acid | human metabolite; mouse metabolite; Saccharomyces cerevisiae metabolite |
| 3-chlorodibenzofuran | 3-chlorodibenzofuran: structure given in first source | ||
| kaempferol | 7-hydroxyflavonol; flavonols; tetrahydroxyflavone | antibacterial agent; geroprotector; human blood serum metabolite; human urinary metabolite; human xenobiotic metabolite; plant metabolite | |
| 7-bromoindirubin-3'-oxime | 7-bromoindirubin-3'-oxime: has mild protein kinase inhibitory activity; induces caspase-independent cell death; structure in first source |