Evidence map›Paper›PMID 32975614›Full record

ArticleCellular and molecular life sciences : CMLS2021

TRAF6-mediated ubiquitination of MST1/STK4 attenuates the TLR4-NF-κB signaling pathway in macrophages.

Kyung-Hye Roh, Yeojin Lee, Je-Hyun Yoon, Danbi Lee, Eunju Kim, Eunchong Park, In Young Lee, Tae Sung Kim, Hyun Kyu Song, Jaekyoon Shin and 2 more

Open access · greenAbstract read
In one paragraph

Article in Cellular and molecular life sciences : CMLS, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.

0numbers the graph read from it
0cells of the map it votes in
11citing papers in PubMed
0.6field-weighted citation impact, top 32% 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

11 citing papers in PubMed, 17 citations in OpenAlex.

  1. Review
  2. Article
  3. Article
  4. Molecular Mechanism of TRAF6 in Malignant Proliferation of Human NK/T Cell Lymphoma Cell HANK1.Mediterranean journal of hematology and infectious diseases · 2025
    Article
  5. Review
  6. Article
  7. Article
  8. MST1/2 in inflammation and immunity.Cell adhesion & migration · 2023
    Review
  9. Review
  10. Article
  11. 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

12 authors at 4 institutions in 3 countries.

Kyung-Hye RohDepartment of Life Sciences, Korea University, Seoul, 02841, Korea.
Yeojin LeeDepartment of Life Sciences, Korea University, Seoul, 02841, Korea.
Je-Hyun YoonDepartment of Biochemistry and Molecular Biology, Medical University of South Carolina, Charleston, SC, 29425, USA.
Danbi LeeDepartment of Life Sciences, Korea University, Seoul, 02841, Korea.
Eunju KimDepartment of Life Sciences, Korea University, Seoul, 02841, Korea.
Eunchong ParkDepartment of Life Sciences, Korea University, Seoul, 02841, Korea.
In Young LeeDepartment of Life Sciences, Korea University, Seoul, 02841, Korea.
Tae Sung KimDepartment of Life Sciences, Korea University, Seoul, 02841, Korea.
Hyun Kyu SongDepartment of Life Sciences, Korea University, Seoul, 02841, Korea.
Jaekyoon ShinDepartment of Molecular Cell Biology, Samsung Biomedical Research Institute, Sungkyunkwan University School of Medicine, Suwon, 16419, Korea.
Dae-Sik LimDepartment of Biological Sciences, National Creative Research Initiatives Center, Biomedical Research Center, Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology, Daejeon, 305-701, Korea.
Eui-Ju ChoiDepartment of Life Sciences, Korea University, Seoul, 02841, Korea. ejchoi@korea.ac.kr.ORCID http://orcid.org/0000-0002-3642-0432
Korea University · KRKorea Advanced Institute of Science and Technology · KRMedical University of South Carolina · USSamsung (South Korea) · KR

Funding

Ministry of Science and ICT of Korea 2016H1A2A1907478Ministry of Science and ICT of Korea NRF-2020R1A2C2011392
6 · The paper itself

Abstract

Pattern-recognition receptors including Toll-like receptors (TLRs) recognize invading pathogens and trigger an immune response in mammals. Here we show that mammalian ste20-like kinase 1/serine/threonine kinase 4 (MST1/STK4) functions as a negative regulator of lipopolysaccharide (LPS)-induced activation of the TLR4-NF-κB signaling pathway associated with inflammation. Myeloid-specific genetic ablation of MST1/STK4 increased the susceptibility of mice to LPS-induced septic shock. Ablation of MST1/STK4 also enhanced NF-κB activation triggered by LPS in bone marrow-derived macrophages (BMDMs), leading to increased production of proinflammatory cytokines by these cells. Furthermore, MST1/STK4 inhibited TRAF6 autoubiquitination as well as TRAF6-mediated downstream signaling induced by LPS. In addition, we found that TRAF6 mediates the LPS-induced activation of MST1/STK4 by catalyzing its ubiquitination, resulting in negative feedback regulation by MST1/STK4 of the LPS-induced pathway leading to cytokine production in macrophages. Together, our findings suggest that MST1/STK4 functions as a negative modulator of the LPS-induced NF-κB signaling pathway during macrophage activation.

Indexed as

AnimalsCells, CulturedCytokinesHEK293 CellsHippo KinasesHumansLipopolysaccharidesMacrophage ActivationMacrophagesMiceMice, Inbred C57BLMice, KnockoutMice, TransgenicNF-kappa BProtein Serine-Threonine KinasesSepsisCytokinesHippo KinasesLipopolysaccharidesNF-kappa BProtein Serine-Threonine KinasesSequestosome-1 ProteinSqstm1 protein, mouseStk4 protein, mouseTlr4 protein, mouseTNF Receptor-Associated Factor 6Toll-Like Receptor 4LipopolysaccharidesMST1/STK4NF-κBTRAF6

Identifiers

PMID32975614
PMCPMC11071754
OpenAlexW3087889094

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.