Evidence map›Paper›PMID 22215675›Full record

ArticleThe Journal of biological chemistry2012

Wilms tumor gene on X chromosome (WTX) inhibits degradation of NRF2 protein through competitive binding to KEAP1 protein.

Nathan D Camp, Richard G James, David W Dawson, Feng Yan, James M Davison, Scott A Houck, Xiaobo Tang, Ning Zheng, Michael B Major, Randall T Moon

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

Article in The Journal of biological chemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 74 papers.

0numbers the graph read from it
0cells of the map it votes in
74citing papers in PubMed
3.6field-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

74 citing papers in PubMed, 130 citations in OpenAlex.

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  18. Targeting NRF2 to promote epithelial repair.Biochemical Society transactions · 2023
    Review
  19. Article
  20. Article

14 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

10 authors at 5 institutions in 1 country.

Nathan D CampHoward Hughes Medical Institute, Department of Pharmacology, Institute for Stem Cell and Regenerative Medicine, University of Washington School of Medicine, Seattle, Washington 98195, USA.
Richard G James
David W Dawson
Feng Yan
James M Davison
Scott A Houck
Xiaobo Tang
Ning Zheng
Michael B Major
Randall T Moon
University of Washington · USUNC Lineberger Comprehensive Cancer CenterUniversity of North Carolina at Chapel Hill · USHoward Hughes Medical Institute · USUCLA Jonsson Comprehensive Cancer Center

Funding

TRAINING IN MOLECULAR AND CELLULAR BIOLOGYT32GM007270 · NIGMS · UNIVERSITY OF WASHINGTON · PI RAIBLE, DAVID W · 1985 to 2020
$21.0M
Structural Studies of cullin-based ubiquitin ligasesR01CA107134 · NCI · UNIVERSITY OF WASHINGTON · PI ZHENG, NING · 2004 to 2013
$3.0M
In vivo role of BTK-mediated inhibition of Wnt/b-catenin signaling during hematopR00HL103768 · NHLBI · SEATTLE CHILDREN'S HOSPITAL · PI JAMES, RICHARD GOFF · 2012 to 2014
$717k
Howard Hughes Medical InstituteNCI NIH HHS R01 CA107134NHLBI NIH HHS R00 HL103768NIGMS NIH HHS T32 GM007270NIGMS NIH HHS T32 GM07270
6 · The paper itself

Abstract

WTX is a tumor suppressor protein that is lost or mutated in up to 30% of cases of Wilms tumor. Among its known functions, WTX interacts with the β-transducin repeat containing family of ubiquitin ligase adaptors and promotes the ubiquitination and degradation of the transcription factor β-catenin, a key control point in the WNT/β-catenin signaling pathway. Here, we report that WTX interacts with a second ubiquitin ligase adaptor, KEAP1, which functions to regulate the ubiquitination of the transcription factor NRF2, a key control point in the antioxidant response. Surprisingly, we find that unlike its ability to promote the ubiquitination of β-catenin, WTX inhibits the ubiquitination of NRF2. WTX and NRF2 compete for binding to KEAP1, and thus loss of WTX leads to rapid ubiquitination and degradation of NRF2 and a reduced response to cytotoxic insult. These results expand our understanding of the molecular mechanisms of WTX and reveal a novel regulatory mechanism governing the antioxidant response.

Indexed as

Adaptor Proteins, Signal TransducingAntioxidantsbeta-Transducin Repeat-Containing ProteinsBinding, CompetitiveChromosomes, Human, XHEK293 CellsHumansIntracellular Signaling Peptides and ProteinsKelch-Like ECH-Associated Protein 1NF-E2-Related Factor 2PhosphorylationRNA, Small InterferingSerineTranscriptional ActivationTumor Suppressor ProteinsUbiquitinationAdaptor Proteins, Signal TransducingAMER1 protein, humanAntioxidantsbeta-Transducin Repeat-Containing ProteinsBTRC protein, humanIntracellular Signaling Peptides and ProteinsKEAP1 protein, humanKelch-Like ECH-Associated Protein 1NFE2L2 protein, humanNF-E2-Related Factor 2RNA, Small InterferingSerineTumor Suppressor Proteins

Identifiers

PMID22215675
PMCPMC3307315
OpenAlexW2085103300

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC
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.