Evidence map›Paper›PMID 37632105›Full record

ArticleViruses2023

MDM2 Influences ACE2 Stability and SARS-CoV-2 Uptake.

Quirin Emslander, Karsten Krey, Sabri Hamad, Susanne Maidl, Lila Oubraham, Joshua Hesse, Alexander Henrici, Katharina Austen, Julia Mergner, Vincent Grass and 1 more

Open access · goldAbstract read
In one paragraph

Article in Viruses, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed, 1 pooled it
1.7field-weighted citation impact, top 16% 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

7 citing papers in PubMed, 1 synthesis or guideline pooled it, 9 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. Article
  4. Article
  5. Review
  6. Article
  7. 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

11 authors at 2 institutions in 2 countries.

Quirin EmslanderInstitute of Virology, School of Medicine, Technical University of Munich (TUM), 81675 Munich, Germany.
Karsten KreyInstitute of Virology, School of Medicine, Technical University of Munich (TUM), 81675 Munich, Germany.ORCID 0000-0002-1280-4722
Sabri HamadInstitute of Virology, School of Medicine, Technical University of Munich (TUM), 81675 Munich, Germany.
Susanne MaidlInstitute of Virology, School of Medicine, Technical University of Munich (TUM), 81675 Munich, Germany.
Lila OubrahamInstitute of Virology, School of Medicine, Technical University of Munich (TUM), 81675 Munich, Germany.
Joshua HesseInstitute of Virology, School of Medicine, Technical University of Munich (TUM), 81675 Munich, Germany.
Alexander HenriciInstitute of Virology, School of Medicine, Technical University of Munich (TUM), 81675 Munich, Germany.
Katharina AustenInstitute of Virology, School of Medicine, Technical University of Munich (TUM), 81675 Munich, Germany.
Julia MergnerBayBioMS@MRI-Bavarian Center for Biomolecular Mass Spectrometry at Klinikum Rechts der Isar, Technical University of Munich, 81675 Munich, Germany.
Vincent GrassInstitute of Virology, School of Medicine, Technical University of Munich (TUM), 81675 Munich, Germany.ORCID 0000-0001-7710-4789
Andreas PichlmairInstitute of Virology, School of Medicine, Technical University of Munich (TUM), 81675 Munich, Germany.ORCID 0000-0002-0166-1367
Technical University of Munich · DEAarhus University · DK

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Angiotensin-converting enzyme 2 (ACE2) is the central entry receptor for SARS-CoV-2. However, surprisingly little is known about the effects of host regulators on ACE2 localization, expression, and the associated influence on SARS-CoV-2 infection. Here we identify that ACE2 expression levels are regulated by the E3 ligase MDM2 and that MDM2 levels indirectly influence infection with SARS-CoV-2. Genetic depletion of MDM2 elevated ACE2 expression levels, which strongly promoted infection with all SARS-CoV-2 isolates tested. SARS-CoV-2 spike-pseudotyped viruses and the uptake of non-replication-competent virus-like particles showed that MDM2 affects the viral uptake process. MDM2 ubiquitinates Lysine 788 of ACE2 to induce proteasomal degradation, and degradation of this residue led to higher ACE2 expression levels and superior virus particle uptake. Our study illustrates that cellular regulators of ACE2 stability, such as MDM2, play an important role in defining the infection capabilities of SARS-CoV-2.

Indexed as

COVID-19SARS-CoV-2Angiotensin-Converting Enzyme 2Biological TransportHumansLysineProto-Oncogene Proteins c-mdm2Angiotensin-Converting Enzyme 2LysineMDM2 protein, humanProto-Oncogene Proteins c-mdm2angiotensin-converting enzyme 2 (ACE2)MDM2SARS-CoV-2 uptakesevere acute respiratory syndrome coronavirus type 2 (SARS-CoV-2)ubiquitination

Identifiers

PMID37632105
PMCPMC10459000
OpenAlexW4385978718

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.