Evidence map›Paper›PMID 28453520›Full record

ArticlePLoS genetics2017

WDR23 regulates NRF2 independently of KEAP1.

Jacqueline Y Lo, Brett N Spatola, Sean P Curran

Open access · goldAbstract read
In one paragraph

Article in PLoS genetics, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 67 papers.

0numbers the graph read from it
0cells of the map it votes in
67citing papers in PubMed
4.1field-weighted citation impact, top 5% 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

67 citing papers in PubMed, 109 citations in OpenAlex.

  1. Article
  2. Review
  3. Review
  4. LIN-23 AffectsbioRxiv : the preprint server for biology · 2026
    Article
  5. Review
  6. Article
  7. Article
  8. Article
  9. Article
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  11. Article
  12. Review
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  15. Article
  16. Article
  17. Review
  18. Article
  19. The Role of NRF2 in Trinucleotide Repeat Expansion Disorders.Antioxidants (Basel, Switzerland) · 2024
    Review
  20. Article

7 more citing papers are in PubMed but not listed here.

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

3 authors at 1 institution in 1 country.

Jacqueline Y LoUniversity of Southern California, Leonard Davis School of Gerontology, Los Angeles, California, United States of America.
Brett N SpatolaUniversity of Southern California, Leonard Davis School of Gerontology, Los Angeles, California, United States of America.
Sean P CurranUniversity of Southern California, Leonard Davis School of Gerontology, Los Angeles, California, United States of America.ORCID 0000-0001-7791-6453
University of Southern California · US

Funding

Enhancing and expanding the CGC Strain CollectionP40OD010440 · OD · UNIVERSITY OF MINNESOTA · PI Aric L Daul, Ann E. Rougvie · 2012 to 2026
$7.5M
Novel roles for Maf1 as a central regulator of lipid homeostasisR01GM109028 · NIGMS · UNIVERSITY OF SOUTHERN CALIFORNIA · PI CURRAN, SEAN P · 2014 to 2018
$1.8M
Training in Genetic, Molecular and Cellular BiologyT32GM067587 · NIGMS · UNIVERSITY OF SOUTHERN CALIFORNIA · PI STALLCUP, MICHAEL R · 2003 to 2012
$1.8M
Evolutionarily conserved mechanisms of lifespan regulationR00AG032308 · NIA · UNIVERSITY OF SOUTHERN CALIFORNIA · PI CURRAN, SEAN P · 2011 to 2013
$746k
NIA NIH HHS R00 AG032308NIGMS NIH HHS R01 GM109028NIGMS NIH HHS T32 GM067587NIH HHS P40 OD010440
6 · The paper itself

Abstract

Cellular adaptation to stress is essential to ensure organismal survival. NRF2/NFE2L2 is a key determinant of xenobiotic stress responses, and loss of negative regulation by the KEAP1-CUL3 proteasome system is implicated in several chemo- and radiation-resistant cancers. Advantageously using C. elegans alongside human cell culture models, we establish a new WDR23-DDB1-CUL4 regulatory axis for NRF2 activity that operates independently of the canonical KEAP1-CUL3 system. WDR23 binds the DIDLID sequence within the Neh2 domain of NRF2 to regulate its stability; this regulation is not dependent on the KEAP1-binding DLG or ETGE motifs. The C-terminal domain of WDR23 is highly conserved and involved in regulation of NRF2 by the DDB1-CUL4 complex. The addition of WDR23 increases cellular sensitivity to cytotoxic chemotherapeutic drugs and suppresses NRF2 in KEAP1-negative cancer cell lines. Together, our results identify WDR23 as an alternative regulator of NRF2 proteostasis and uncover a cellular pathway that regulates NRF2 activity and capacity for cytoprotection independently of KEAP1.

Indexed as

Amino Acid MotifsAnimalsCaenorhabditis elegansCaenorhabditis elegans ProteinsCell Line, TumorCullin ProteinsGene Expression Regulation, NeoplasticHumansKelch-Like ECH-Associated Protein 1NeoplasmsNF-E2-Related Factor 2Proteasome Endopeptidase ComplexProtein BindingRepressor ProteinsSignal TransductionCaenorhabditis elegans ProteinsCUL-3 protein, C elegansCullin ProteinsKelch-Like ECH-Associated Protein 1NF-E2-Related Factor 2Proteasome Endopeptidase ComplexRepressor ProteinsWDR-23 protein, C elegans

Identifiers

PMID28453520
PMCPMC5428976
OpenAlexW2608930323

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.