Evidence map›Paper›PMID 34272357›Full record

ArticleCell death & disease2021

PLEKHO2 inhibits TNFα-induced cell death by suppressing RIPK1 activation.

Chenchen Zhou, Xueli Zhang, Cuiping Yang, Yuan He, Luo Zhang

Open access · goldAbstract read
In one paragraph

Article in Cell death & disease, 2021. 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
0.2field-weighted citation impact, top 57% 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

5 citing papers in PubMed, 5 citations in OpenAlex.

  1. Review
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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.

Chenchen Zhou *Department of Biomedical Engineering, the Fifth medical Centre, Chinese PLA General Hospital, Beijing, 100071, China.
Xueli Zhang *Department of pathology, the Fifth medical Centre, Chinese PLA General Hospital, Beijing, 100071, China.
Cuiping Yang *Department of Respiratory and Critical Care Medicine, the Fifth medical Centre, Chinese PLA General Hospital, Beijing, 100071, China.
Yuan HeDepartment of Respiratory and Critical Care Medicine, the Fifth medical Centre, Chinese PLA General Hospital, Beijing, 100071, China.
Luo ZhangDepartment of Biomedical Engineering, the Fifth medical Centre, Chinese PLA General Hospital, Beijing, 100071, China. marbleluo@126.com.ORCID 0000-0002-7688-5955
Chinese PLA General Hospital · CN

Funding

Natural Science Foundation of Beijing Municipality (Beijing Natural Science Foundation) 5192021
6 · The paper itself

Abstract

Receptor interaction protein kinase 1 (RIPK1) plays a diverse role in tumor necrosis factor α (TNFα) signalings. The ubiquitination of RIPK1 is essential for NF-κB activation, whereas its kinase activity promotes apoptosis and necroptosis. However, the mechanisms underlying have not been fully illuminated. Here we report that PH domain-containing family O member 2 (PLEKHO2) inhibits RIPK1-dependent cell death and is necessary for NF-κB activation in response to TNFα. Cells of PLKEHO2 deficiency are more susceptible to TNF-α induced apoptosis and necroptosis with increased RIPK1 activation, which is consistent with the observation that the susceptibility of PLEKHO2-/- cells is effectively prevented by treatment of RIPK1 kinase inhibitor. Moreover, PLEKHO2 deficient cells exhibit compromised RIPK1 ubiquitination and NF-κB activation in response to TNFα. Ultimately, PLEKHO2-deficient mice display greatly increased hepatotoxicity and lethality after TNFα-induced hepatitis. In summary, our study revealed that PLEKHO2 is a novel inhibitor of apoptosis and necroptosis, which plays a key role in regulating RIPK1 ubiquitination and activation.

Indexed as

ApoptosisAnimalsCycloheximideEnzyme ActivationFemaleFibroblastsHEK293 CellsHumansIntercellular Signaling Peptides and ProteinsLiverMaleMiceMice, Inbred C57BLNecroptosisNF-kappa BReceptor-Interacting Protein Serine-Threonine KinasesCycloheximideIntercellular Signaling Peptides and ProteinsNF-kappa BReceptor-Interacting Protein Serine-Threonine KinasesRipk1 protein, mouseTumor Necrosis Factor-alpha

Identifiers

PMID34272357
PMCPMC8285381
OpenAlexW3180370966

What OpenQuestion holds

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LicenceCC BY
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.