Evidence map›Paper›PMID 30996091›Full record

ArticleJournal of virology2019

Adenovirus E1B 55-Kilodalton Protein Targets SMARCAL1 for Degradation during Infection and Modulates Cellular DNA Replication.

Reshma Nazeer, Fadi S I Qashqari, Abeer S Albalawi, Ann Liza Piberger, Maria Teresa Tilotta, Martin L Read, Siyuan Hu, Simon Davis, Christopher J McCabe, Eva Petermann and 1 more

Open access · bronzeAbstract read
In one paragraph

Article in Journal of virology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed
1.8field-weighted citation impact, top 14% 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, 12 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

11 authors at 3 institutions in 1 country.

Reshma NazeerInstitute of Cancer & Genomic Sciences, College of Medical and Dental Sciences, The University of Birmingham, Birmingham, United Kingdom.
Fadi S I QashqariInstitute of Cancer & Genomic Sciences, College of Medical and Dental Sciences, The University of Birmingham, Birmingham, United Kingdom.
Abeer S AlbalawiInstitute of Cancer & Genomic Sciences, College of Medical and Dental Sciences, The University of Birmingham, Birmingham, United Kingdom.
Ann Liza PibergerInstitute of Cancer & Genomic Sciences, College of Medical and Dental Sciences, The University of Birmingham, Birmingham, United Kingdom.
Maria Teresa TilottaInstitute of Cancer & Genomic Sciences, College of Medical and Dental Sciences, The University of Birmingham, Birmingham, United Kingdom.
Martin L ReadInstitute of Metabolism & Systems Research, College of Medical and Dental Sciences, The University of Birmingham, Birmingham, United Kingdom.
Siyuan HuInstitute of Cancer & Genomic Sciences, College of Medical and Dental Sciences, The University of Birmingham, Birmingham, United Kingdom.
Simon DavisInstitute of Cancer & Genomic Sciences, College of Medical and Dental Sciences, The University of Birmingham, Birmingham, United Kingdom.
Christopher J McCabeInstitute of Metabolism & Systems Research, College of Medical and Dental Sciences, The University of Birmingham, Birmingham, United Kingdom.
Eva PetermannInstitute of Cancer & Genomic Sciences, College of Medical and Dental Sciences, The University of Birmingham, Birmingham, United Kingdom.
Andrew S TurnellInstitute of Cancer & Genomic Sciences, College of Medical and Dental Sciences, The University of Birmingham, Birmingham, United Kingdom A.S.Turnell@bham.ac.uk.ORCID 0000-0002-8738-8882
University of Birmingham · GBMRC University of Glasgow Centre for Virus Research · GBUniversity of Oxford · GB

Funding

Biotechnology and Biological Sciences Research Council BB/J014532/1Biotechnology and Biological Sciences Research Council BB/M01116X/1Medical Research Council MR/P000509/1
6 · The paper itself

Abstract

Here, we show that the cellular DNA replication protein and ATR substrate SMARCAL1 is recruited to viral replication centers early during adenovirus infection and is then targeted in an E1B-55K/E4orf6- and cullin RING ligase-dependent manner for proteasomal degradation. In this regard, we have determined that SMARCAL1 is phosphorylated at S123, S129, and S173 early during infection in an ATR- and CDK-dependent manner, and that pharmacological inhibition of ATR and CDK activities attenuates SMARCAL1 degradation. SMARCAL1 recruitment to viral replication centers was shown to be largely dependent upon SMARCAL1 association with the RPA complex, while Ad-induced SMARCAL1 phosphorylation also contributed to SMARCAL1 recruitment to viral replication centers, albeit to a limited extent. SMARCAL1 was found associated with E1B-55K in adenovirus E1-transformed cells. Consistent with its ability to target SMARCAL1, we determined that E1B-55K modulates cellular DNA replication. As such, E1B-55K expression initially enhances cellular DNA replication fork speed but ultimately leads to increased replication fork stalling and the attenuation of cellular DNA replication. Therefore, we propose that adenovirus targets SMARCAL1 for degradation during infection to inhibit cellular DNA replication and promote viral replication.

Indexed as

DNA ReplicationVirus ReplicationA549 CellsAdenoviridae InfectionsAdenovirus E1B ProteinsAdenoviruses, HumanAtaxia Telangiectasia Mutated ProteinsCyclin-Dependent KinasesDNA-Binding ProteinsDNA DamageDNA HelicasesHumansNuclear ProteinsPhosphorylationProteasome Endopeptidase ComplexSignal TransductionAdenovirus E1B ProteinsAtaxia Telangiectasia Mutated ProteinsATR protein, humanCyclin-Dependent KinasesDNA-Binding ProteinsDNA HelicasesNuclear ProteinsProteasome Endopeptidase ComplexSMARCAL1 protein, humanUbiquitinadenovirusesDNA damage response

Identifiers

PMID30996091
PMCPMC6580949
OpenAlexW2938308159

What OpenQuestion holds

Textmetadata
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.