Evidence map›Paper›PMID 37126714›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2023

The PRAK-NRF2 axis promotes the differentiation of Th17 cells by mediating the redox homeostasis and glycolysis.

Ziheng Zhao, Yan Wang, Yuhan Gao, Yurong Ju, Ye Zhao, Zhaofei Wu, Shuaixin Gao, Boyang Zhang, Xuewen Pang, Yu Zhang and 1 more

Open access · greenAbstract read
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.

0numbers the graph read from it
0cells of the map it votes in
32citing papers in PubMed
7.4field-weighted citation impact, top 2% 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

32 citing papers in PubMed, 48 citations in OpenAlex.

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  15. Ferroptosis of T cell in inflammation and tumour immunity.Clinical and translational medicine · 2025
    Review
  16. Article
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  19. Everolimus alleviates CD4GeroScience · 2024
    Article
  20. CD4Trends in cancer · 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

11 authors at 2 institutions in 1 country.

Ziheng ZhaoDepartment of Immunology, School of Basic Medical Sciences, National Health Commission Key Laboratory of Medical Immunology, Peking University, Beijing 100191, China.
Yan WangFirst Clinical Medical College, Shanxi Medical University, Taiyuan 030001, Shanxi, China.
Yuhan GaoDepartment of Immunology, School of Basic Medical Sciences, National Health Commission Key Laboratory of Medical Immunology, Peking University, Beijing 100191, China.
Yurong JuDepartment of Immunology, School of Basic Medical Sciences, National Health Commission Key Laboratory of Medical Immunology, Peking University, Beijing 100191, China.
Ye ZhaoDepartment of Immunology, School of Basic Medical Sciences, National Health Commission Key Laboratory of Medical Immunology, Peking University, Beijing 100191, China.
Zhaofei WuDepartment of Immunology, School of Basic Medical Sciences, National Health Commission Key Laboratory of Medical Immunology, Peking University, Beijing 100191, China.
Shuaixin GaoCenter for Precision Medicine Multi-Omics Research, Peking University Health Science Center, Beijing 102206, China.ORCID 0000-0003-2815-5461
Boyang ZhangDepartment of Immunology, School of Basic Medical Sciences, National Health Commission Key Laboratory of Medical Immunology, Peking University, Beijing 100191, China.
Xuewen PangDepartment of Immunology, School of Basic Medical Sciences, National Health Commission Key Laboratory of Medical Immunology, Peking University, Beijing 100191, China.
Yu ZhangDepartment of Immunology, School of Basic Medical Sciences, National Health Commission Key Laboratory of Medical Immunology, Peking University, Beijing 100191, China.ORCID 0000-0001-5383-3207
Wei WangDepartment of Immunology, School of Basic Medical Sciences, National Health Commission Key Laboratory of Medical Immunology, Peking University, Beijing 100191, China.ORCID 0000-0002-4923-5412
Peking University · CNShanxi Medical University · CN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Oxidative stress is a key feature in both chronic inflammation and cancer. P38 regulated/activated protein kinase (PRAK) deficiency can cause functional disorders in neutrophils and macrophages under high oxidative stress, but the precise mechanisms by which PRAK regulates reactive oxygen species (ROS) elimination and its potential impact on CD4+ T helper subset function are unclear. The present study reveals that the PRAK-NF-E2-related factor 2(NRF2) axis is essential for maintaining the intracellular redox homeostasis of T helper 17(Th17) cells, thereby promoting Th17 cell differentiation and antitumor effects. Through mechanistic analysis, we identify NRF2 as a novel protein substrate of PRAK and find that PRAK enhances the stability of the NRF2 protein through phosphorylation NRF2 Serine(S) 558 independent of protein ubiquitination. High accumulation of cellular ROS caused by loss of PRAK disrupts both glycolysis and PKM2-dependent phosphorylation of STAT3, which subsequently impairs the differentiation of Th17 cells. As a result,

Indexed as

Encephalomyelitis, Autoimmune, ExperimentalProtein KinasesAnimalsCell DifferentiationGlycolysisHomeostasisIntracellular Signaling Peptides and ProteinsMiceMice, KnockoutNF-E2-Related Factor 2Oxidation-ReductionProtein Serine-Threonine KinasesReactive Oxygen SpeciesTh17 CellsIntracellular Signaling Peptides and ProteinsMAP-kinase-activated kinase 5NF-E2-Related Factor 2Protein KinasesProtein Serine-Threonine KinasesReactive Oxygen SpeciesglycolysisNRF2PRAKROSTh17

Identifiers

PMID37126714
PMCPMC10175746
OpenAlexW4367626396

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.