Evidence map›Paper›PMID 41332654›Full record

ArticlebioRxiv : the preprint server for biology2025

The electrophilic metabolite of kynurenine, kynurenine-CKA, targets C151 in Keap1 to derepress Nrf2.

Jialin Feng, Mara Carreño, Hannah Jung, Sharadha Dayalan Naidu, Nicole Arroyo Diaz, Abel D Ang, Bhargavi Kulkarni, Dorothy Kisielewski, Takafumi Suzuki, Masayuki Yamamoto and 6 more

Abstract readPreprint
PubMed Full text at PMC Publisher
In one paragraph

Article in bioRxiv : the preprint server for biology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
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

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

16 authors.

Jialin FengJacqui Wood Cancer Centre, Division of Cancer Research, School of Medicine, University of Dundee, Dundee, UK.
Mara CarreñoDepartment of Pathology, School of Medicine, The University of Alabama at Birmingham, Birmingham, AL, USA.
Hannah JungDepartment of Chemistry and Biochemistry, Villanova University, Villanova, PA, USA.
Sharadha Dayalan NaiduJacqui Wood Cancer Centre, Division of Cancer Research, School of Medicine, University of Dundee, Dundee, UK.
Nicole Arroyo DiazDepartment of Pathology, School of Medicine, The University of Alabama at Birmingham, Birmingham, AL, USA.
Abel D AngJacqui Wood Cancer Centre, Division of Cancer Research, School of Medicine, University of Dundee, Dundee, UK.
Bhargavi KulkarniDepartment of Pathology, School of Medicine, The University of Alabama at Birmingham, Birmingham, AL, USA.
Dorothy KisielewskiJacqui Wood Cancer Centre, Division of Cancer Research, School of Medicine, University of Dundee, Dundee, UK.
Takafumi SuzukiDepartment of Biochemistry and Molecular Biology, Tohoku Medical Megabank Organization, Tohoku University, Sendai, Japan.
Masayuki YamamotoDepartment of Biochemistry and Molecular Biology, Tohoku Medical Megabank Organization, Tohoku University, Sendai, Japan.
John D HayesJacqui Wood Cancer Centre, Division of Cancer Research, School of Medicine, University of Dundee, Dundee, UK.
Tadashi HondaDepartment of Chemistry and Institute of Chemical Biology & Drug Discovery, Stony Brook University, Stony Brook, NY, USA.
Beatriz Leon-RuizInnate Cells and Th2 Immunity Section, Laboratory of Allergic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
Aimee L EgglerDepartment of Chemistry and Biochemistry, Villanova University, Villanova, PA, USA.
Dario A VitturiDepartment of Pathology, School of Medicine, The University of Alabama at Birmingham, Birmingham, AL, USA.ORCID 0000-0003-0354-4567
Albena T Dinkova-KostovaJacqui Wood Cancer Centre, Division of Cancer Research, School of Medicine, University of Dundee, Dundee, UK.

Funding

IMMUNOLOGIC DISEASES AND BASIC IMMUNOLOGYT32AI007051 · NIAID · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI Laurie Ellen Harrington · 1985 to 2026
$13.1M
Kynurenine-dependent redox signaling at the interface between innate and adaptive immunityR01AI178864 · NIAID · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI VITTURI, DARIO A · 2023 to 2024
$1.1M
Formation, metabolism and cell signaling actions of tryptophan catabolism-derived electrophilesR35GM152083 · NIGMS · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI Dario A Vitturi · 2024 to 2026
$1.1M
NIAID NIH HHS R01 AI178864NIAID NIH HHS T32 AI007051NIGMS NIH HHS R35 GM152083
6 · The paper itself

Abstract

The Kelch-like ECH-associated protein 1 / Nuclear factor-erythroid 2 p45-related factor 2 (Keap1/Nrf2) system responds to a wide array of structurally diverse small molecules, of both exogenous and endogenous origin, by inducing a robust cytoprotective program that allows adaptation during oxidative, metabolic and inflammatory stress. Here, we report that exposure to the tryptophan metabolite kynurenine and its electrophilic derivative kynurenine-carboxyketoalkene (Kyn-CKA) leads to an increase in the abundance of transcription factor Nrf2 and induction of Nrf2-target genes, including NAD(P)H:quinone oxidoreductase 1 (NQO1), in murine and human cells. Additionally, both kynurenine and Kyn-CKA activate the aryl hydrocarbon receptor (AhR). Using cellular thermal shift assays, we found that Kyn-CKA increases the thermal stability of Keap1-mCherry fusion protein, but not free mCherry, indicating target engagement of Keap1, the principal repressor of Nrf2. The use of purified recombinant BTB domain of Keap1 and its C151S mutant counterpart revealed that Kyn-CKA reacts with wild-type, but not C151S mutant, Keap1-BTB, and at a much faster rate than with the small molecule thiol

Identifiers

PMID41332654
PMCPMC12667871

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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.