Evidence map›Paper›PMID 24681086›Full record

ReviewBiotechnology advances2014

Monitoring Keap1-Nrf2 interactions in single live cells.

Liam Baird, Sam Swift, David Llères, Albena T Dinkova-Kostova

Open access · hybridAbstract readReview
In one paragraph

Review in Biotechnology advances, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 73 papers.

0numbers the graph read from it
0cells of the map it votes in
73citing papers in PubMed
6.3field-weighted citation impact, top 3% 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

73 citing papers in PubMed, 156 citations in OpenAlex.

  1. Article
  2. International journal of molecular sciences · 2026
    Review
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  4. Article
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  7. Article
  8. Article
  9. Nanomedicine-Driven Modulation of Reductive Stress for Cancer Therapy.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025
    Review
  10. Article
  11. Review
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  13. Article
  14. Article
  15. Review
  16. Article
  17. FructusBiomedical reports · 2024
    Article
  18. Review
  19. Article
  20. Review

13 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

4 authors at 3 institutions in 3 countries.

Liam BairdJacqui Wood Cancer Centre, Division of Cancer Research, Medical Research Institute, University of Dundee, Dundee DD1 9SY Scotland, UK.
Sam SwiftMicroscopy Facility, College of Life Sciences, University of Dundee, Dundee DD1 5EH Scotland, UK.
David LlèresInstitute of Molecular Genetics of Montpellier, 34293 Montpellier Cedex 5, France.
Albena T Dinkova-KostovaJacqui Wood Cancer Centre, Division of Cancer Research, Medical Research Institute, University of Dundee, Dundee DD1 9SY Scotland, UK; Department of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA. Electronic address: a.dinkovakostova@dundee.ac.uk.
University of Dundee · GBInstitut de Génétique Moléculaire de Montpellier · FRJohns Hopkins Medicine · US

Funding

Cancer Research UK 10270Cancer Research UK C20953/A10270Medical Research Council
6 · The paper itself

Abstract

The transcription factor NF-E2 p45-related factor 2 (Nrf2) and its negative regulator Kelch-like ECH associated protein 1 (Keap1) control the expression of nearly 500 genes with diverse cytoprotective functions. Keap1, a substrate adaptor protein for Cullin3/Rbx1 ubiquitin ligase, normally continuously targets Nrf2 for degradation, but loses this ability in response to electrophiles and oxidants (termed inducers). Consequently, Nrf2 accumulates and activates transcription of its downstream target genes. Many inducers are phytochemicals, and cruciferous vegetables represent one of the richest sources of inducer activity among the most commonly used edible plants. Here we summarize the discovery of the isothiocyanate sulforaphane as a potent inducer which reacts with cysteine sensors of Keap1, leading to activation of Nrf2. We then describe the development of a quantitative Förster resonance energy transfer (FRET)-based methodology combined with multiphoton fluorescence lifetime imaging microscopy (FLIM) to investigate the interactions between Keap1 and Nrf2 in single live cells, and the effect of sulforaphane, and other cysteine-reactive inducers, on the dynamics of the Keap1-Nrf2 protein complex. We present the experimental evidence for the "cyclic sequential attachment and regeneration" or "conformation cycling" model of Keap1-mediated Nrf2 degradation. Finally, we discuss the implications of this mode of regulation of Nrf2 for achieving a fine balance under normal physiological conditions, and the consequences and mechanisms of disrupting this balance for tumor biology.

Indexed as

Intracellular Signaling Peptides and ProteinsNF-E2 Transcription Factor, p45 SubunitSignal TransductionAnimalsBinding SitesCell LineFluorescence Resonance Energy TransferHumansKelch-Like ECH-Associated Protein 1MiceRatsSingle-Cell AnalysisIntracellular Signaling Peptides and ProteinsKEAP1 protein, humanKelch-Like ECH-Associated Protein 1NF-E2 Transcription Factor, p45 SubunitCytoprotective enzymesFLIMFRETKeap1Nrf2Sulforaphane

Identifiers

PMID24681086
PMCPMC4165437
OpenAlexW2126184403

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.