Evidence map›Paper›PMID 25349783›Full record

ArticleFEBS open bio2014

The activation mechanism of the aryl hydrocarbon receptor (AhR) by molecular chaperone HSP90.

Noriko Tsuji, Kana Fukuda, Yuhtaroh Nagata, Hirotaka Okada, Asami Haga, Shiori Hatakeyama, Shiho Yoshida, Tomoya Okamoto, Miki Hosaka, Kazuhiro Sekine and 5 more

Erratum issuedOpen access · goldAbstract read
In one paragraph

Article in FEBS open bio, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 65 papers.

0numbers the graph read from it
0cells of the map it votes in
65citing papers in PubMed
4.6field-weighted citation impact, top 6% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

65 citing papers in PubMed, 105 citations in OpenAlex.

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  16. The Role of Aryl Hydrocarbon Receptor in Bone Biology.International journal of tryptophan research : IJTR · 2024
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  18. Review
  19. Article
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5 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

15 authors at 3 institutions in 1 country.

Noriko TsujiDepartment of Life Science, Graduate School and Faculty of Engineering Science, Akita University, Akita 010-8502, Japan.
Kana FukudaDepartment of Life Science, Graduate School and Faculty of Engineering Science, Akita University, Akita 010-8502, Japan.
Yuhtaroh NagataDepartment of Life Science, Graduate School and Faculty of Engineering Science, Akita University, Akita 010-8502, Japan.
Hirotaka OkadaDepartment of Life Science, Graduate School and Faculty of Engineering Science, Akita University, Akita 010-8502, Japan.
Asami HagaDepartment of Life Science, Graduate School and Faculty of Engineering Science, Akita University, Akita 010-8502, Japan.
Shiori HatakeyamaDepartment of Life Science, Graduate School and Faculty of Engineering Science, Akita University, Akita 010-8502, Japan.
Shiho YoshidaDepartment of Life Science, Graduate School and Faculty of Engineering Science, Akita University, Akita 010-8502, Japan.
Tomoya OkamotoDepartment of Life Science, Graduate School and Faculty of Engineering Science, Akita University, Akita 010-8502, Japan.
Miki HosakaDepartment of Life Science, Graduate School and Faculty of Engineering Science, Akita University, Akita 010-8502, Japan.
Kazuhiro SekineDepartment of Life Science, Graduate School and Faculty of Engineering Science, Akita University, Akita 010-8502, Japan.
Kei OhtakaDepartment of Life Science, Graduate School and Faculty of Engineering Science, Akita University, Akita 010-8502, Japan.
Soh YamamotoDepartment of Microbiology, Sapporo Medical University School of Medicine, Sapporo 060-8556, Japan.
Michiro OtakaDepartment of Gastroenterology, Juntendo University School of Medicine, Bunkyo-Ku, Tokyo 113-8421, Japan.
Ewa GraveDepartment of Life Science, Graduate School and Faculty of Engineering Science, Akita University, Akita 010-8502, Japan.
Hideaki ItohDepartment of Life Science, Graduate School and Faculty of Engineering Science, Akita University, Akita 010-8502, Japan.
Akita University · JPJuntendo University · JPSapporo Medical University · JP

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The aryl hydrocarbon receptor is a member of the nuclear receptor superfamily that associates with the molecular chaperone HSP90 in the cytoplasm. The activation mechanism of the AhR is not yet fully understood. It has been proposed that after binding of ligands such as 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), 3methylcholanthrene (3-MC), or β-naphthoflavone (β-NF), the AhR dissociates from HSP90 and translocates to the nucleus. It has also been hypothesized that the AhR translocates to the nucleus and forms a complex with HSP90 and other co-chaperones. There are a few reports about the direct association or dissociation of AhR and HSP90 due to difficulties in purifying AhR. We constructed and purified the PAS domain from AhR. Binding of the AhR-PAS domain to β-NF affinity resin suggested that it possesses ligand-binding affinity. We demonstrated that the AhR-PAS domain binds to HSP90 and the association is not affected by ligand binding. The ligand 17-DMAG inhibited binding of HSP90 to GST-PAS. In an immunoprecipitation assay, HSP90 was co-immunoprecipitated with AhR both in the presence or absence of ligand. Endogenous AhR decreased in the cytoplasm and increased in the nucleus of HeLa cells 15 min after treatment with ligand. These results suggested that the ligand-bound AhR is translocated to nucleus while in complex with HSP90. We used an in situ proximity ligation assay to confirm whether AhR was translocated to the nucleus alone or together with HSP90. HSP90 was co-localized with AhR after the nuclear translocation. It has been suggested that the ligand-bound AhR was translocated to the nucleus with HSP90. Activated AhR acts as a transcription factor, as shown by the transcription induction of the gene CYP1A1 8 h after treatment with β-NF.

Indexed as

17-DMAG, 17-(dimethylaminoethylamino)-17-demethoxygeldanamycin, dimethylsulfoxide3-MC, 3-methylcholanthreneAhRAhR, aryl hydrocarbon receptorArnt, AhR nuclear translocatorAryl hydrocarbon receptorbHLH, basic helix-loop-helixCYP1A1, cytochrome P450 1A1DAPI, 4′,6-diamidino-2-phenylindoleDEPC, dihydrochloride, diethylpyrocarbonatedDioxin receptorGST, glutathione, glutathione S-transferaseHSP90HSP90, 90-kDa of heat shock proteinIPTG, isopropyl-1-thio-β-d-galactopyranosideMolecular chaperoneNLS, nuclear localization signalPAS, per-arnt-simPLA, proximity ligation assayRT-PCR, reverse transcription-polymerase chain reactionTCDD, 2,3,7,8-tetrachlorodibenzo-p-dioxinXAP2, hepatitis B virus X-associated proteinXRE, xenobiotic responsible elementβ-NF, β-naphthoflavone

Identifiers

PMID25349783
PMCPMC4208086
OpenAlexW1976470222

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.