Evidence map›Paper›PMID 26189595›Full record

ArticleScientific reports2015

Polyubiquitination of Transforming Growth Factor β-activated Kinase 1 (TAK1) at Lysine 562 Residue Regulates TLR4-mediated JNK and p38 MAPK Activation.

I-Ting Chen, Pang-Hung Hsu, Wan-Ching Hsu, Nien-Jung Chen, Ping-Hui Tseng

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Scientific reports, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.

0numbers the graph read from it
0cells of the map it votes in
34citing papers in PubMed
2.3field-weighted citation impact, top 12% 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

34 citing papers in PubMed, 54 citations in OpenAlex.

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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

5 authors at 1 institution in 1 country.

I-Ting ChenInstitute of Biochemistry and Molecular Biology, School of Life Sciences, National Yang-Ming University, Taipei 11221, Taiwan (ROC).
Pang-Hung Hsu1] Institute of Biochemistry and Molecular Biology, School of Life Sciences, National Yang-Ming University, Taipei 11221, Taiwan (ROC) [2] Institute of Bioscience and Biotechnology, College of Life Sciences, National Taiwan Ocean University, Keelung20224, Taiwan (ROC).
Wan-Ching HsuInstitute of Biochemistry and Molecular Biology, School of Life Sciences, National Yang-Ming University, Taipei 11221, Taiwan (ROC).
Nien-Jung Chen1] Institute of Microbiology and Immunology, School of Life Sciences, National Yang-Ming University, Taipei 11221, Taiwan (ROC) [2] Infection and Immunity Research Center, National Yang-Ming University, Taipei 11221, Taiwan (ROC).
Ping-Hui Tseng1] Institute of Biochemistry and Molecular Biology, School of Life Sciences, National Yang-Ming University, Taipei 11221, Taiwan (ROC) [2] Infection and Immunity Research Center, National Yang-Ming University, Taipei 11221, Taiwan (ROC).
National Yang Ming Chiao Tung University · TW

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Toll-like receptor 4 (TLR4) plays an important role in innate immunity by eliciting inflammation. Upon receptor engagement, transforming growth factor β-activated kinase 1 (TAK1) is an essential mediator that transmits a signal from the receptor to downstream effectors, IκB kinase (IKK) and the mitogen-activated protein kinases (MAPKs), which control the production of inflammatory cytokines. However, the association between phosphorylation and ubiquitination of TAK1 is not yet clear. Here, we examined the crosstalk between phosphorylation and polyubiquitination of TAK1 and further investigated the mechanism of distinct activation of MAPKs and IKK. Inhibition of TAK1 phosphorylation enhanced Lys63-linked polyubiquitination of TAK1. Conversely, ubiquitin modification was counteracted by phospho-mimic TAK1 mutant, T(184,187)D. Moreover, using LC-MS analysis, Lys562 of TAK1 was identified as a novel Lys63-linked ubiquitination site and as the key residue in the feedback regulation. Mutation of Lys562 of TAK1 leads to a decrease in TAK1 phosphorylation and specific inhibition of the MAPK pathway, but has no effect on formation of the TAK1-containing complex. Our findings demonstrate a feedback loop for phosphorylation and ubiquitination of TAK1, indicating a dynamic regulation between TAK1 polyubiquitiantion and phosphorylated activation, and the molecular mechanism by which IKK and MAPKs are differentially activated in the TLR4 pathway.

Indexed as

Adaptor Proteins, Signal TransducingAmino Acid SequenceAnimalsCell LineCytokinesEnzyme ActivationHumansI-kappa B KinaseJNK Mitogen-Activated Protein KinasesLysineMAP Kinase Kinase Kinase 7MAP Kinase Kinase KinasesMiceMolecular Sequence DataMutationp38 Mitogen-Activated Protein KinasesAdaptor Proteins, Signal TransducingCytokinesI-kappa B KinaseJNK Mitogen-Activated Protein KinasesLysineMAP Kinase Kinase Kinase 7MAP Kinase Kinase Kinasesp38 Mitogen-Activated Protein KinasesTAB1 protein, humanTNF Receptor-Associated Factor 6Toll-Like Receptor 4Transforming Growth Factor beta

Identifiers

PMID26189595
PMCPMC4507259
OpenAlexW2268158936

What OpenQuestion holds

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Read underepoch 390

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.