Evidence map›Paper›PMID 29717933›Full record

ReviewPhysiological reviews2018

The KEAP1-NRF2 System: a Thiol-Based Sensor-Effector Apparatus for Maintaining Redox Homeostasis.

Masayuki Yamamoto, Thomas W Kensler, Hozumi Motohashi

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

Review in Physiological reviews, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1,045 papers, 4 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
1,045citing papers in PubMed, 4 pooled it
47.0field-weighted citation impact, top 1% 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

1,045 citing papers in PubMed, 4 syntheses or guidelines pooled it, 1,791 citations in OpenAlex.

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  11. Emerging microbes & infections · 2026
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985 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 2 countries.

Masayuki YamamotoDepartment of Medical Biochemistry, Graduate School of Medicine, Tohoku University , Sendai , Japan ; Department of Pharmacology & Chemical Biology, University of Pittsburgh , Pittsburgh, Pennsylvania ; and Department of Gene Expression Regulation, Institute of Development, Aging and Cancer, Tohoku University , Sendai , Japan.ORCID 0000-0002-9073-9436
Thomas W KenslerDepartment of Medical Biochemistry, Graduate School of Medicine, Tohoku University , Sendai , Japan ; Department of Pharmacology & Chemical Biology, University of Pittsburgh , Pittsburgh, Pennsylvania ; and Department of Gene Expression Regulation, Institute of Development, Aging and Cancer, Tohoku University , Sendai , Japan.
Hozumi MotohashiDepartment of Medical Biochemistry, Graduate School of Medicine, Tohoku University , Sendai , Japan ; Department of Pharmacology & Chemical Biology, University of Pittsburgh , Pittsburgh, Pennsylvania ; and Department of Gene Expression Regulation, Institute of Development, Aging and Cancer, Tohoku University , Sendai , Japan.
University of Pittsburgh · US

Funding

Targeting Nrf2 for Cancer ChemopreventionR35CA197222 · NCI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI KENSLER, THOMAS W · 2015 to 2021
$6.7M
NCI NIH HHS R35 CA197222
6 · The paper itself

Abstract

The Kelch-like ECH-associated protein 1-NF-E2-related factor 2 (KEAP1-NRF2) system forms the major node of cellular and organismal defense against oxidative and electrophilic stresses of both exogenous and endogenous origins. KEAP1 acts as a cysteine thiol-rich sensor of redox insults, whereas NRF2 is a transcription factor that robustly transduces chemical signals to regulate a battery of cytoprotective genes. KEAP1 represses NRF2 activity under quiescent conditions, whereas NRF2 is liberated from KEAP1-mediated repression on exposure to stresses. The rapid inducibility of a response based on a derepression mechanism is an important feature of the KEAP1-NRF2 system. Recent studies have unveiled the complexities of the functional contributions of the KEAP1-NRF2 system and defined its broader involvement in biological processes, including cell proliferation and differentiation, as well as cytoprotection. In this review, we describe historical milestones in the initial characterization of the KEAP1-NRF2 system and provide a comprehensive overview of the molecular mechanisms governing the functions of KEAP1 and NRF2, as well as their roles in physiology and pathology. We also refer to the clinical significance of the KEAP1-NRF2 system as an important prophylactic and therapeutic target for various diseases, particularly aging-related disorders. We believe that controlled harnessing of the KEAP1-NRF2 system is a key to healthy aging and well-being in humans.

Indexed as

Amino Acid SequenceCarcinogenesisCytoprotectionGene Expression RegulationHomeostasisHumansInflammationKelch-Like ECH-Associated Protein 1Maf Transcription FactorsNF-E2-Related Factor 2Oxidation-ReductionKEAP1 protein, humanKelch-Like ECH-Associated Protein 1Maf Transcription FactorsNFE2L2 protein, humanNF-E2-Related Factor 2

Identifiers

PMID29717933
PMCPMC9762786
OpenAlexW2799290037

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.