Scientific background: |
AHR(aryl hydrocarbon receptor), also called bHLHe76, is a member of the family of basic helix-loop-helix transcription factors. AhR is a cytosolic transcription factor that is normally inactive, bound to several co-chaperones. The AHR gene is mapped on 7p21.1. Estrogenic actions of AHR agonists were detected in wildtype ovariectomized mouse uteri, but were absent in Ahr -/- or Er-alpha -/- ovariectomized mice. Complex assembly and ubiquitin ligase activity of CUL4B(AHR) in vitro and in vivo are dependent on the AHR ligand. In the CUL4B(AHR) complex, ligand-activated AHR acts as a substrate-specific adaptor component that targets sex steroid receptors for degradation. Cd4-positive cells from mice lacking Ahr developed Th17 responses but failed to produce Il22 and did not show enhanced Th17 development. Activation of Ahr during induction of EAE accelerated disease onset and increased pathology in wildtype mice, but not in Ahr -/- mice. The TDO-AHR pathway is active in human brain tumors and is associated with malignant progression and poor survival. Ahr activity within ROR-gamma-t-positive ILC could be induced by dietary ligands such as those contained in vegetables of the family Brassicaceae. |
References: |
1. Andersson, P., McGuire, J., Rubio, C., Gradin, K., Whitelaw, M. L., Pettersson, S., Hanberg, A., Poellinger, L. A constitutively active dioxin/aryl hydrocarbon receptor induces stomach tumors. Proc. Nat. Acad. Sci. 99: 9990-9995, 2002.
2. Ema, M., Matsushita, N., Sogawa, K., Ariyama, T., Inazawa, J., Nemoto, T., Ota, M., Oshimura, M., Fujii-Kuriyama, Y. Human arylhydrocarbon receptor: functional expression and chromosomal assignment to 7p21. J. Biochem. 116: 845-851, 1994.
3. Le Beau, M. M., Carver, L. A., Espinosa, R., III, Schmidt, J. V., Bradfield, C. A. Chromosomal localization of the human AHR locus encoding the structural gene for the Ah receptor to 7p21-p15. Cytogenet. Cell Genet. 66: 172-176, 1994.
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