Evidence map›Paper›PMID 35856559›Full record

ArticlemBio2022

Ubiquitination of SARS-CoV-2 NSP6 and ORF7a Facilitates NF-κB Activation.

Hironori Nishitsuji, Satoko Iwahori, Mariko Ohmori, Kunitada Shimotohno, Takayuki Murata

Open access · goldAbstract read
In one paragraph

Article in mBio, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
39citing papers in PubMed, 1 pooled it
5.0field-weighted citation impact, top 3% 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

39 citing papers in PubMed, 1 synthesis or guideline pooled it, 51 citations in OpenAlex.

  1. Pooled it
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  17. NSP6 of SARS-CoV-2 Dually Regulates Autophagic-Lysosomal Degradation.International journal of molecular sciences · 2025
    Article
  18. Review
  19. Review
  20. Classification and regulatory interactions of key transcription factors in COVID-19.Frontiers in cellular and infection microbiology · 2025
    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

5 authors at 2 institutions in 1 country.

Hironori NishitsujiDepartment of Virology and Parasitology, Fujita Health University School of Medicine, Aichi, Japan.ORCID 0000-0002-2872-1550
Satoko IwahoriDepartment of Virology and Parasitology, Fujita Health University School of Medicine, Aichi, Japan.
Mariko OhmoriDepartment of Virology and Parasitology, Fujita Health University School of Medicine, Aichi, Japan.
Kunitada ShimotohnoThe Research Center for Hepatitis and Immunology, National Center for Global Health and Medicine, Chiba, Japan.
Takayuki MurataDepartment of Virology and Parasitology, Fujita Health University School of Medicine, Aichi, Japan.ORCID 0000-0001-7228-0839
Fujita Health University · JPNational Center for Global Health and Medicine · JP

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Patients with severe coronavirus disease 2019 tend to have high levels of proinflammatory cytokines, which eventually lead to cytokine storm and the development of acute respiratory distress syndrome. However, the detailed molecular mechanisms of proinflammatory cytokine production remain unknown. Here, we screened severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) genes and found that nonstructural protein 6 (NSP6) and open reading frame 7a (ORF7a) activated the NF-κB pathway. NSP6 and ORF7a interacted with transforming growth factor β-activated kinase 1 (TAK1), and knockout (KO) of TAK1 or NF-κB essential modulator (NEMO) abolished NF-κB activation by NSP6 and ORF7a. Interestingly, K61 of NSP6 was conjugated to K63-linked polyubiquitin chains by the E3 ubiquitin ligase tripartite motif-containing 13, and this polyubiquitination of NSP6 appeared crucial for recruitment of NEMO to the NSP6-TAK1 complex and NF-κB activation. On the other hand, ring finger protein 121 (RNF121) was required for the polyubiquitination of ORF7a. Knockdown of RNF121 significantly decreased ORF7a binding of TAK1 and NEMO, resulting in the suppression of NF-κB activation. Taken together, our results provide novel molecular insights into the pathogenesis of SARS-CoV-2 and the host immune response to SARS-CoV-2 infection.

Indexed as

COVID-19NF-kappa BCytokinesHumansOpen Reading FramesSARS-CoV-2UbiquitinationCytokinesNF-kappa BinflammationNF-κBSARS-CoV-2

Identifiers

PMID35856559
PMCPMC9426613
OpenAlexW4286210172

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.