Evidence map›Paper›PMID 10409767›Full record

ArticleMolecular and cellular biology1999

Multiple roles of ligand in transforming the dioxin receptor to an active basic helix-loop-helix/PAS transcription factor complex with the nuclear protein Arnt.

M J Lees, M L Whitelaw

Open access · greenAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Molecular and cellular biology, 1999. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.

0numbers the graph read from it
0cells of the map it votes in
32citing papers in PubMed
2.2field-weighted citation impact, top 12% 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

32 citing papers in PubMed, 96 citations in OpenAlex.

  1. Article
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  3. Review
  4. Review
  5. Article
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  7. Article
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  9. Article
  10. The Role of the Neuroprotective Factor Npas4 in Cerebral Ischemia.International journal of molecular sciences · 2015
    Review
  11. Indole and Tryptophan Metabolism: Endogenous and Dietary Routes to Ah Receptor Activation.Drug metabolism and disposition: the biological fate of chemicals · 2015
    Review
  12. Article
  13. Article
  14. Identification of stanniocalcin 2 as a novel aryl hydrocarbon receptor target gene.The Journal of pharmacology and experimental therapeutics · 2013
    Article
  15. Article
  16. Review
  17. Article
  18. Article
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

2 authors at 1 institution in 1 country.

M J LeesDepartment of Biochemistry, University of Adelaide, Adelaide 5005, South Australia, Australia.
M L Whitelaw
The University of Adelaide · AU

Funding

Wellcome Trust
6 · The paper itself

Abstract

The dioxin receptor is a ligand-activated transcription factor belonging to an emerging class of basic helix-loop-helix/PAS proteins which show interaction with the molecular chaperone hsp90 in their latent states and require heterodimerization with a general cofactor, Arnt, to form active DNA binding complexes. Upon binding of polycyclic aromatic hydrocarbons typified by dioxin, the dioxin receptor translocates from the cytoplasm to the nucleus to allow interaction with Arnt. Here we have bypassed the nuclear translocation step by creating a cell line which expresses a constitutively nuclear dioxin receptor, which we find remains in a latent form, demonstrating that ligand has functional roles beyond initiating nuclear import of the receptor. Treatment of the nuclear receptor with dioxin induces dimerization with Arnt to form an active transcription factor complex, while in stark contrast, treatment with the hsp90 ligand geldanamycin results in rapid degradation of the receptor. Inhibition of degradation by a proteasome inhibitor allowed geldanamycin to transform the nuclear dioxin receptor to a heterodimer with Arnt (DR-Arnt). Our results indicate that unchaperoned dioxin receptor is extremely labile and is consistent with a concerted nuclear mechanism for receptor activation whereby hsp90 is released from the ligand-bound dioxin receptor concomitant with Arnt dimerization. Strikingly, artificial transformation of the receptor by geldanamycin provided a DR-Arnt complex capable of binding DNA but incapable of stimulating transcription. Limited proteolysis of DR-Arnt heterodimers indicated different conformations for dioxin versus geldanamycin-transformed receptors. Our studies of intracellular dioxin receptor transformation indicate that ligand plays multiple mechanistic roles during receptor activation, being important for nuclear translocation, transformation to an Arnt heterodimer, and maintenance of a structural integrity key for transcriptional activation.

Indexed as

DNA-Binding ProteinsHelix-Loop-Helix MotifsAdrenal GlandsAmino Acid SequenceAnimalsAryl Hydrocarbon Receptor Nuclear TranslocatorBenzoquinonesCell Line, TransformedCell NucleusDimerizationHSP90 Heat-Shock ProteinsHumansKidneyLactams, MacrocyclicLigandsLiver Neoplasms, ExperimentalARNT protein, humanArnt protein, mouseAryl Hydrocarbon Receptor Nuclear TranslocatorBenzoquinonesDNA-Binding ProteinsgeldanamycinHSP90 Heat-Shock ProteinsLactams, MacrocyclicLigandsMacromolecular SubstancesQuinonesReceptors, Aryl HydrocarbonRecombinant Fusion ProteinsTranscription Factors

Identifiers

PMID10409767
PMCPMC84430
OpenAlexW2141323846

What OpenQuestion holds

Textmetadata
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.