Evidence map›Paper›PMID 24912676›Full record

ArticleMolecular and cellular biology2014

Direct interaction between the WD40 repeat protein WDR-23 and SKN-1/Nrf inhibits binding to target DNA.

Chi K Leung, Koichi Hasegawa, Ying Wang, Andrew Deonarine, Lanlan Tang, Johji Miwa, Keith P Choe

RetractedOpen access · bronzeAbstract readRetracted Publication
In one paragraph

Article in Molecular and cellular biology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It has been retracted, and should not be counted. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
1.0field-weighted citation impact, top 28% 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

5 citing papers in PubMed, 14 citations in OpenAlex.

  1. Article
  2. Sphingosine Kinase Regulates Neuropeptide Secretion During the Oxidative Stress-Response Through Intertissue Signaling.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2018
    Article
  3. Article
  4. Review
  5. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

7 authors at 2 institutions in 2 countries.

Chi K LeungDepartment of Biology and Genetics Institute, University of Florida, Gainesville, Florida, USA.
Koichi HasegawaDepartment of Environmental Biology, College of Bioscience and Biotechnology, Chubu University, Kasugai, Aichi, Japan.
Ying WangDepartment of Biology and Genetics Institute, University of Florida, Gainesville, Florida, USA.
Andrew DeonarineDepartment of Biology and Genetics Institute, University of Florida, Gainesville, Florida, USA.
Lanlan TangDepartment of Biology and Genetics Institute, University of Florida, Gainesville, Florida, USA.
Johji MiwaDepartment of Environmental Biology, College of Bioscience and Biotechnology, Chubu University, Kasugai, Aichi, Japan Academy of Arts and Sciences, Chubu University, Kasugai, Aichi, Japan.
Keith P ChoeDepartment of Biology and Genetics Institute, University of Florida, Gainesville, Florida, USA kchoe@ufl.edu.
University of Florida · USChubu University · JP

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

SKN-1/Nrf transcription factors activate cytoprotective genes in response to reactive small molecules and strongly influence stress resistance, longevity, and development. The molecular mechanisms of SKN-1/Nrf regulation are poorly defined. We previously identified the WD40 repeat protein WDR-23 as a repressor of Caenorhabditis elegans SKN-1 that functions with a ubiquitin ligase to presumably target the factor for degradation. However, SKN-1 activity and nuclear accumulation are not always correlated, suggesting that there could be additional regulatory mechanisms. Here, we integrate forward genetics and biochemistry to gain insights into how WDR-23 interacts with and regulates SKN-1. We provide evidence that WDR-23 preferentially regulates one of three SKN-1 variants through a direct interaction that is required for normal stress resistance and development. Homology modeling predicts that WDR-23 folds into a β-propeller, and we identify the top of this structure and four motifs at the termini of SKN-1c as essential for the interaction. Two of these SKN-1 motifs are highly conserved in human Nrf1 and Nrf2 and two directly interact with target DNA. Lastly, we demonstrate that WDR-23 can block the ability of SKN-1c to interact with DNA sequences of target promoters identifying a new mechanism of regulation that is independent of the ubiquitin proteasome system, which can become occupied with damaged proteins during stress.

Indexed as

AnimalsAnimals, Genetically ModifiedCaenorhabditis elegansCaenorhabditis elegans ProteinsDNA-Binding ProteinsDNA, ProtozoanGene Expression RegulationLarvaLongevityProtein BindingProtein FoldingRepressor ProteinsStress, PhysiologicalTranscription FactorsCaenorhabditis elegans ProteinsDNA-Binding ProteinsDNA, ProtozoanRepressor Proteinsskn-1 protein, C elegansTranscription FactorsWDR-23 protein, C elegans

Identifiers

PMID24912676
PMCPMC4135592
OpenAlexW2168087091

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.