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Pathway Description
Ahr Signal Transduction Pathway
Bos taurus
Category:
Protein Pathway
Sub-Categories:
Gene Regulatory
Cellular Response
Created: 2018-08-31
Last Updated: 2019-08-16
The aryl hydrocarbon receptor, known as AHR, is a normally cytosolic transcription factor that can bind to foreign compounds such as flavonoids and indoles from foods, as well as synthetic ligands including polychlorobiphenyls (PCBs) and polychlorinated dibenzo-p-dioxins (PCDD). This includes 2,3,7,8-tetrachlorodibenzodioxin (TCDD), which is the ligand shown in this pathway.
AHR interacts with heat shock protein 90 (HSP90AA1), which acts as a chaperone for it. After this association, the ligand, in this case TCDD, can form a covalent bond with the complex in the cell's cytoplasm. This binding causes AHR and the rest of the complex to translocate into the nucleus of the cell. Once in the nucleus, the heat shock protein dissociates, leaving binding sites which the AHR nuclear translocator (ARNT) then binds to. Finally, the AHR/ARNT complex can interact, either directly or indirectly, with the DNA, in this case specifically a dioxin response element. With other ligands, the complex will bind to the equivalent DNA that corresponds to the genes that allow metabolism of the ligand.
References
Ahr Signal Transduction Pathway References
Hara S, Kobayashi C, Imura N: Molecular cloning of cDNAs encoding hypoxia-inducible factor (HIF)-1alpha and -2alpha of bovine arterial endothelial cells. Biochim Biophys Acta. 1999 May 14;1445(2):237-43. doi: 10.1016/s0167-4781(99)00048-2.
Pubmed: 10320777
Sakurai S, Shimizu T, Ohto U: The crystal structure of the AhRR-ARNT heterodimer reveals the structural basis of the repression of AhR-mediated transcription. J Biol Chem. 2017 Oct 27;292(43):17609-17616. doi: 10.1074/jbc.M117.812974. Epub 2017 Sep 13.
Pubmed: 28904176
This pathway was propagated using PathWhiz -
Pon, A. et al. Pathways with PathWhiz (2015) Nucleic Acids Res. 43(Web Server issue): W552–W559.
Propagated from SMP0063771
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