The role of DNA-binding and ARNT dimerization on the nucleo-cytoplasmic translocation of the aryl hydrocarbon receptor.
Active Transport, Cell Nucleus
Aryl Hydrocarbon Receptor Nuclear Translocator
/ chemistry
Basic Helix-Loop-Helix Transcription Factors
/ chemistry
Binding Sites
Cell Nucleus
/ metabolism
DNA
/ metabolism
Hep G2 Cells
Humans
MCF-7 Cells
Protein Binding
Protein Multimerization
Receptors, Aryl Hydrocarbon
/ chemistry
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
14 09 2021
14 09 2021
Historique:
received:
24
06
2021
accepted:
24
08
2021
entrez:
15
9
2021
pubmed:
16
9
2021
medline:
15
12
2021
Statut:
epublish
Résumé
The human aryl hydrocarbon receptor (AHR) is predominantly located in the cytoplasm, while activation depends on its nuclear translocation. Binding to endogenous or xenobiotic ligands terminates the basal nucleo-cytoplasmic shuttling and stabilizes an exclusive nuclear population. The precise mechanisms that facilitate such stable nuclear accumulation remain to be clarified as essential step in the activation cascade. In this study, we have tested whether the sustained nuclear compartmentalization of ligand-bound or basal AHR might further require heterodimerization with the AHR-nuclear translocator (ARNT) and binding to the cognate XRE-motif. Mutagenesis of the DNA-binding motif or of selected individual residues in the ARNT-binding motif did not lead to any variation in AHR's nucleo-cytoplasmic distribution. In response to ligands, all mutants were retained in the nucleus demonstrating that the stable compartmentalization of activated AHR in the nucleus is neither dependent on interactions with DNA, nor ARNT. Knocking down the ARNT gene using small interfering RNA confirmed that ARNT does not play any role in the intracellular trafficking of AHR.
Identifiants
pubmed: 34521881
doi: 10.1038/s41598-021-97507-w
pii: 10.1038/s41598-021-97507-w
pmc: PMC8440571
doi:
Substances chimiques
AHR protein, human
0
ARNT protein, human
0
Basic Helix-Loop-Helix Transcription Factors
0
Receptors, Aryl Hydrocarbon
0
Aryl Hydrocarbon Receptor Nuclear Translocator
138391-32-9
DNA
9007-49-2
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
18194Informations de copyright
© 2021. The Author(s).
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