Evidence map›Paper›PMID 29789521›Full record

ArticleCell death & disease2018

Triad3a induces the degradation of early necrosome to limit RipK1-dependent cytokine production and necroptosis.

Norah A Alturki, Scott McComb, Ardeshir Ariana, Dikchha Rijal, Robert G Korneluk, Shao-Cong Sun, Emad Alnemri, Subash Sad

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

Article in Cell death & disease, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.

0numbers the graph read from it
0cells of the map it votes in
14citing papers in PubMed
1.1field-weighted citation impact, top 23% 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

14 citing papers in PubMed, 22 citations in OpenAlex.

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  14. Roles of ubiquitin in autophagy and cell death.Seminars in cell & developmental biology · 2019
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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

8 authors at 5 institutions in 3 countries.

Norah A AlturkiDepartment of Biochemistry, Microbiology, and Immunology, Faculty of Medicine, University of Ottawa, Ottawa, Canada.
Scott McCombHuman Health and Therapeutics, National Research Council of Canada, Ottawa, Canada.
Ardeshir ArianaDepartment of Biochemistry, Microbiology, and Immunology, Faculty of Medicine, University of Ottawa, Ottawa, Canada.
Dikchha RijalDepartment of Biochemistry, Microbiology, and Immunology, Faculty of Medicine, University of Ottawa, Ottawa, Canada.
Robert G KornelukDepartment of Biochemistry, Microbiology, and Immunology, Faculty of Medicine, University of Ottawa, Ottawa, Canada.
Shao-Cong SunDepartment of Immunology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Emad AlnemriThomas Jefferson University, Philadelphia, PA, USA.
Subash SadDepartment of Biochemistry, Microbiology, and Immunology, Faculty of Medicine, University of Ottawa, Ottawa, Canada. subash.sad@uottawa.ca.
University of Ottawa · CAInstitute of Infection and Immunity · CANational Research Council Canada · CAThe University of Texas MD Anderson Cancer Center · USThomas Jefferson University · US

Funding

Cysteine Proteases in ApoptosisR01AR055398 · NIAMS · THOMAS JEFFERSON UNIVERSITY · PI ALNEMRI, EMAD S · 2008 to 2018
$4.2M
NIAMS NIH HHS R01 AR055398
6 · The paper itself

Abstract

Understanding the molecular signaling in programmed cell death is vital to a practical understanding of inflammation and immune cell function. Here we identify a previously unrecognized mechanism that functions to downregulate the necrosome, a central signaling complex involved in inflammation and necroptosis. We show that RipK1 associates with RipK3 in an early necrosome, independent of RipK3 phosphorylation and MLKL-induced necroptotic death. We find that formation of the early necrosome activates K48-ubiquitin-dependent proteasomal degradation of RipK1, Caspase-8, and other necrosomal proteins. Our results reveal that the E3-ubiquitin ligase Triad3a promotes this negative feedback loop independently of typical RipK1 ubiquitin editing enzymes, cIAPs, A20, or CYLD. Finally, we show that Triad3a-dependent necrosomal degradation limits necroptosis and production of inflammatory cytokines. These results reveal a new mechanism of shutting off necrosome signaling and may pave the way to new strategies for therapeutic manipulation of inflammatory responses.

Indexed as

ApoptosisProteolysisAnimalsCytokinesInhibitor of Apoptosis ProteinsLysineMice, Inbred C57BLNecrosisProteasome Endopeptidase ComplexProtein BindingReceptor-Interacting Protein Serine-Threonine KinasesUbiquitinationUbiquitin-Protein LigasesCytokinesInhibitor of Apoptosis ProteinsLysineProteasome Endopeptidase ComplexReceptor-Interacting Protein Serine-Threonine KinasesRipk1 protein, mouseRipk3 protein, mouseRNF216 protein, mouseUbiquitin-Protein Ligases

Identifiers

PMID29789521
PMCPMC5964080
OpenAlexW2803164013

What OpenQuestion holds

Textmetadata
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.