Evidence map›Paper›PMID 34299054›Full record

ArticleInternational journal of molecular sciences2021

Nrf2, the Major Regulator of the Cellular Oxidative Stress Response, is Partially Disordered.

Nadun C Karunatilleke, Courtney S Fast, Vy Ngo, Anne Brickenden, Martin L Duennwald, Lars Konermann, Wing-Yiu Choy

Open access · goldAbstract read
In one paragraph

Article in International journal of molecular sciences, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.

0numbers the graph read from it
0cells of the map it votes in
28citing papers in PubMed
2.9field-weighted citation impact, top 8% 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

28 citing papers in PubMed, 49 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Dissecting the Interplay Between NRF2 and BACH1 at CsMBEs.Antioxidants (Basel, Switzerland) · 2025
    Article
  5. Article
  6. Reinforcing Nrf2 Signaling: Help in the Alzheimer's Disease Context.International journal of molecular sciences · 2025
    Review
  7. Gut microbiota and atrial cardiomyopathy.Frontiers in cardiovascular medicine · 2025
    Review
  8. Review
  9. Article
  10. Article
  11. Article
  12. Review
  13. Review
  14. Article
  15. Review
  16. Review
  17. Review
  18. Review
  19. Review
  20. Targeting Nrf2 signaling in dry eye.International journal of ophthalmology · 2024
    Review
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

7 authors at 1 institution in 1 country.

Nadun C KarunatillekeDepartment of Biochemistry, The University of Western Ontario, London, ON N6A 5C1, Canada.
Courtney S FastDepartment of Chemistry, The University of Western Ontario, London, ON N6A 5B7, Canada.
Vy NgoDepartment of Pathology and Laboratory Medicine, The University of Western Ontario, London, ON N6A 5C1, Canada.ORCID 0000-0002-6282-9549
Anne BrickendenDepartment of Biochemistry, The University of Western Ontario, London, ON N6A 5C1, Canada.
Martin L DuennwaldDepartment of Pathology and Laboratory Medicine, The University of Western Ontario, London, ON N6A 5C1, Canada.
Lars KonermannDepartment of Biochemistry, The University of Western Ontario, London, ON N6A 5C1, Canada.
Wing-Yiu ChoyDepartment of Biochemistry, The University of Western Ontario, London, ON N6A 5C1, Canada.
Western University · CA

Funding

Natural Sciences and Engineering Research Council of Canada RGPIN-2018-04243Natural Sciences and Engineering Research Council of Canada RGPIN-2019-06711
6 · The paper itself

Abstract

Nuclear factor erythroid 2-related factor 2 (Nrf2) is a transcription regulator that plays a pivotal role in coordinating the cellular response to oxidative stress. Through interactions with other proteins, such as Kelch-like ECH-associated protein 1 (Keap1), CREB-binding protein (CBP), and retinoid X receptor alpha (RXRα), Nrf2 mediates the transcription of cytoprotective genes critical for removing toxicants and preventing DNA damage, thereby playing a significant role in chemoprevention. Dysregulation of Nrf2 is linked to tumorigenesis and chemoresistance, making Nrf2 a promising target for anticancer therapeutics. However, despite the physiological importance of Nrf2, the molecular details of this protein and its interactions with most of its targets remain unknown, hindering the rational design of Nrf2-targeted therapeutics. With this in mind, we used a combined bioinformatics and experimental approach to characterize the structure of full-length Nrf2 and its interaction with Keap1. Our results show that Nrf2 is partially disordered, with transiently structured elements in its Neh2, Neh7, and Neh1 domains. Moreover, interaction with the Kelch domain of Keap1 leads to protection of the binding motifs in the Neh2 domain of Nrf2, while the rest of the protein remains highly dynamic. This work represents the first detailed structural characterization of full-length Nrf2 and provides valuable insights into the molecular basis of Nrf2 activity modulation in oxidative stress response.

Indexed as

Binding SitesHumansIntrinsically Disordered ProteinsKelch-Like ECH-Associated Protein 1Models, MolecularNF-E2-Related Factor 2Oxidative StressProtein BindingProtein Structure, TertiaryIntrinsically Disordered ProteinsKEAP1 protein, humanKelch-Like ECH-Associated Protein 1NFE2L2 protein, humanNF-E2-Related Factor 2circular dichroismhydrogen/deuterium exchangeintrinsically disorderedKeap1mass spectrometryNrf2nuclear magnetic resonance spectroscopyoxidative stress

Identifiers

PMID34299054
PMCPMC8305528
OpenAlexW3180470416

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.