dc.contributor.author
Haidar, Rashad
dc.contributor.author
Shabo, Reneh
dc.contributor.author
Moeser, Marie
dc.contributor.author
Luch, Andreas
dc.contributor.author
Kugler, Josephine
dc.date.accessioned
2024-02-06T11:37:02Z
dc.date.available
2024-02-06T11:37:02Z
dc.identifier.uri
https://refubium.fu-berlin.de/handle/fub188/42311
dc.identifier.uri
http://dx.doi.org/10.17169/refubium-42036
dc.description.abstract
The human aryl hydrocarbon receptor (AHR) undergoes continuous shuttling between nucleus and cytoplasm. Binding to exogenous or endogenous ligands promotes its rapid nuclear import. The proposed mechanism for the ligand-dependent import is based on exposing the bipartite nuclear localisation signal (NLS) to members of the importin (IMP) superfamily. Among this, the molecular interactions involved in the basal import still need to be clarified. Utilizing fluorescently fused AHR variants, we recapitulated and characterized AHR localization and nucleo-cytoplasmic shuttling in living cells. Analysis of AHR variants carrying NLS point mutations demonstrated a mandatory role of first (13RKRRK17) and second (37KR-R40) NLS segments on the basal import of AHR. Further experiments indicated that ligand-induced import is mainly regulated through the first NLS, while the second NLS is supportive but not essential. Additionally, applying IMPα/β specific inhibitors, ivermectin (IVM) and importazole (IPZ), slowed down the ligand-induced import and, correspondingly, decreased the basal nuclear accumulation of the receptor. In conclusion, our data show that ligand-induced and basal nuclear entry of AHR rely on the same mechanism but are controlled uniquely by the two NLS components.
en
dc.format.extent
11 Seiten
dc.subject
Biochemistry
en
dc.subject
Biotechnology
en
dc.subject
Cell biology
en
dc.subject
Molecular biology
en
dc.subject.ddc
600 Technik, Medizin, angewandte Wissenschaften::610 Medizin und Gesundheit::615 Pharmakologie, Therapeutik
dc.title
The nuclear entry of the aryl hydrocarbon receptor (AHR) relies on the first nuclear localization signal and can be negatively regulated through IMPα/β specific inhibitors
dc.type
Wissenschaftlicher Artikel
dcterms.bibliographicCitation.articlenumber
19668
dcterms.bibliographicCitation.doi
10.1038/s41598-023-47066-z
dcterms.bibliographicCitation.journaltitle
Scientific Reports
dcterms.bibliographicCitation.volume
13
dcterms.bibliographicCitation.url
https://doi.org/10.1038/s41598-023-47066-z
refubium.affiliation
Biologie, Chemie, Pharmazie
refubium.affiliation.other
Institut für Pharmazie
refubium.resourceType.isindependentpub
no
dcterms.accessRights.openaire
open access
dcterms.isPartOf.eissn
2045-2322
refubium.resourceType.provider
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