Evidence map›Paper›PMID 39163853›Full record

ArticleCell chemical biology2025

Human AKR1C3 binds agonists of GPR84 and participates in an expanded polyamine pathway.

Natavan Dudkina, Hyun Bong Park, Deguang Song, Abhishek Jain, Sajid A Khan, Richard A Flavell, Caroline H Johnson, Noah W Palm, Jason M Crawford

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell chemical biology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing 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

5 citing papers in PubMed.

  1. A new branch of mammalian vitamin BThe FEBS journal · 2026
    Article
  2. Review
  3. Article
  4. Review
  5. The microbiome diversifiesbioRxiv : the preprint server for biology · 2024
    Article
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

9 authors.

Natavan DudkinaDepartment of Chemistry, Yale University, New Haven, CT 06520, USA; Institute of Biomolecular Design & Discovery, Yale University, West Haven, CT 06516, USA.
Hyun Bong ParkDepartment of Chemistry, Yale University, New Haven, CT 06520, USA; Institute of Biomolecular Design & Discovery, Yale University, West Haven, CT 06516, USA; Department of Biology, College of Natural Sciences, Gangneung-Wonju National University, Gangneung 25457, Republic of Korea.
Deguang SongDepartment of Immunobiology, Yale School of Medicine, New Haven, CT 06536, USA.
Abhishek JainDepartment of Environmental Health Sciences, Yale School of Public Health, New Haven, CT 06536, USA.
Sajid A KhanDepartment of Surgery, Division of Surgical Oncology, Yale School of Medicine, New Haven, CT 06510, USA.
Richard A FlavellDepartment of Immunobiology, Yale School of Medicine, New Haven, CT 06536, USA; Howard Hughes Medical Institute, Yale School of Medicine, New Haven, CT 06536, USA.
Caroline H JohnsonDepartment of Environmental Health Sciences, Yale School of Public Health, New Haven, CT 06536, USA. Electronic address: caroline.johnson@yale.edu.
Noah W PalmDepartment of Immunobiology, Yale School of Medicine, New Haven, CT 06536, USA. Electronic address: noah.palm@yale.edu.
Jason M CrawfordDepartment of Chemistry, Yale University, New Haven, CT 06520, USA; Institute of Biomolecular Design & Discovery, Yale University, West Haven, CT 06516, USA; Department of Microbial Pathogenesis, Yale School of Medicine, New Haven, CT 06536, USA. Electronic address: jason.crawford@yale.edu.

Funding

Yale Clinical and Translational Science Award (U Component)UL1TR001863 · NCATS · YALE UNIVERSITY · PI John H. Krystal, LUCILA OHNO-MACHADO · 2016 to 2026
$102.9M
Microbial Chemical Sensing and Host ResponsesRM1GM141649 · NIGMS · YALE UNIVERSITY · PI Jason Michael Crawford, Caroline Helen Johnson · 2021 to 2026
$9.0M
NCATS NIH HHS UL1 TR001863NIGMS NIH HHS RM1 GM141649
6 · The paper itself

Abstract

Altered human aldo-keto reductase family 1 member C3 (AKR1C3) expression has been associated with poor prognosis in diverse cancers, ferroptosis resistance, and metabolic diseases. Despite its clinical significance, the endogenous biochemical roles of AKR1C3 remain incompletely defined. Using untargeted metabolomics, we identified a major transformation mediated by AKR1C3, in which a spermine oxidation product "sperminal" is reduced to "sperminol." Sperminal causes DNA damage and activates the DNA double-strand break response, whereas sperminol induces autophagy in vitro. AKR1C3 also pulls down acyl-pyrones and pyrone-211 inhibits AKR1C3 activity. Through G protein-coupled receptor ligand screening, we determined that pyrone-211 is also a potent agonist of the semi-orphan receptor GPR84. Strikingly, mammalian fatty acid synthase produces acyl-pyrones in vitro, and this production is modulated by NADPH. Taken together, our studies support a regulatory role of AKR1C3 in an expanded polyamine pathway and a model linking fatty acid synthesis and NADPH levels to GPR84 signaling.

Indexed as

Aldo-Keto Reductase Family 1 Member C3PolyaminesReceptors, G-Protein-CoupledHumansPyronesAKR1C3 protein, humanAldo-Keto Reductase Family 1 Member C3PolyaminesPyronesReceptors, G-Protein-CoupledAKR1C3autophagycancerfatty acid synthasegenotoxicityGPR84metabolomicsoxidative stresspolyaminesreactive carbonyl species

Identifiers

PMID39163853
PMCPMC11748234

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Registered trials

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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.