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Fig. 1 | Journal of Translational Medicine

Fig. 1

From: Aryl hydrocarbon receptor activation mediates kidney disease and renal cell carcinoma

Fig. 1

AhR transcription in mammalian cells and the putative mechanism of AhR activation. The inactive form of AhR occurs in the cytoplasm as a complex with chaperone proteins, including HSP90, P23 and XAP2. Multiple exogenous and endogenous AhR ligands from the environment, diet, host metabolism and gut microbiome induce a conformational alteration in AhR, exposing the nuclear localization signal to activate nuclear shuttling. Once in the nucleus, AhR forms a heterodimeric complex, with ARNT binding to the XRE sequence motif 5′-GCGTG-3′. This induces the expression of its target genes, such as CYP1A1, CYP1A2, CYP1B1 and COX-2, which are involved in the inflammatory response and xenobiotic metabolism. Furthermore, AhR mediates AhR repressor expression, abrogating the formation of the AhR/ARNT heterodimer and inhibiting its transcriptional activity. Moreover, AhR forms as a Cul4B-based E3 ubiquitin ligase complex, inducing selective protein degradation. AhR regulation signalling can be controlled via nuclear export and subsequent AhR degradation through the ubiquitin–proteasome signalling pathway. In addition to this canonical pathway, signalling through AhR can also be mediated through interactions with other regulatory proteins, such as oestrogen receptor, NF-κB and RB

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