Evidence map›Paper›PMID 22740413›Full record

ArticleJournal of virology2012

Adenovirus regulates sumoylation of Mre11-Rad50-Nbs1 components through a paralog-specific mechanism.

Sook-Young Sohn, Patrick Hearing

Open access · bronzeAbstract read
In one paragraph

Article in Journal of virology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.

0numbers the graph read from it
0cells of the map it votes in
28citing papers in PubMed
1.2field-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

28 citing papers in PubMed, 37 citations in OpenAlex.

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  15. Review
  16. Take your PIKK: tumour viruses and DNA damage response pathways.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2017
    Review
  17. SUMO, a small, but powerful, regulator of double-strand break repair.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2017
    Review
  18. Viral Interplay with the Host Sumoylation System.Advances in experimental medicine and biology · 2017
    Review
  19. Review
  20. The adenovirus E4-ORF3 protein functions as a SUMO E3 ligase for TIF-1γ sumoylation and poly-SUMO chain elongation.Proceedings of the National Academy of Sciences of the United States of America · 2016
    Article
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

2 authors at 1 institution in 1 country.

Sook-Young SohnDepartment of Molecular Genetics and Microbiology, School of Medicine, Stony Brook University, Stony Brook, New York, USA.
Patrick Hearing
Stony Brook University · US

Funding

Regulation of Nuclear Signaling Pathways by the Adenovirus E4-ORF3 ProteinR01CA122677 · NCI · STATE UNIVERSITY NEW YORK STONY BROOK · PI HEARING, PATRICK · 2007 to 2022
$5.2M
NCI NIH HHS CA122677NCI NIH HHS R01 CA122677
6 · The paper itself

Abstract

The Mre11-Rad50-Nbs1 (MRN) complex plays a key role in the DNA damage response, presenting challenges for DNA viruses and retroviruses. To inactivate this complex, adenovirus (Ad) makes use of the E1B-55K and E4-open reading frame 6 (ORF6) proteins for ubiquitin (Ub)-mediated, proteasome-dependent degradation of MRN and the E4-ORF3 protein for relocalization and sequestration of MRN within infected-cell nuclei. Here, we report that Mre11 is modified by the Ub-related modifier SUMO-2 and Nbs1 is modified by both SUMO-1 and SUMO-2. We found that Mre11 and Nbs1 are sumoylated during Ad5 infection and that the E4-ORF3 protein is necessary and sufficient to induce SUMO conjugation. Relocalization of Mre11 and Nbs1 into E4-ORF3 nuclear tracks is required for this modification to occur. E4-ORF3-mediated SUMO-1 conjugation to Nbs1 and SUMO-2 conjugation to Mre11 and Nbs1 are transient during wild-type Ad type 5 (Ad5) infection. In contrast, SUMO-1 conjugation to Nbs1 is stable in cells infected with E1B-55K or E4-ORF6 mutant viruses, suggesting that Ad regulates paralog-specific desumoylation of Nbs1. Inhibition of viral DNA replication blocks deconjugation of SUMO-2 from Mre11 and Nbs1, indicating that a late-phase process is involved in Mre11 and Nbs1 desumoylation. Our results provide direct evidence of Mre11 and Nbs1 sumoylation induced by the Ad5 E4-ORF3 protein and an important example showing that modification of a single substrate by both SUMO-1 and SUMO-2 is regulated through distinct mechanisms. Our findings suggest how E4-ORF3-mediated relocalization of the MRN complex influences the cellular DNA damage response.

Indexed as

Acid Anhydride HydrolasesAdenovirus E1B ProteinsAdenovirus E4 ProteinsAdenoviruses, HumanCell Cycle ProteinsCell NucleusDNA-Binding ProteinsDNA DamageDNA RepairDNA Repair EnzymesHeLa CellsHost-Pathogen InteractionsHumansKineticsMRE11 Homologue ProteinMutant ProteinsAcid Anhydride HydrolasesAdenovirus E1B ProteinsAdenovirus E4 ProteinsCell Cycle ProteinsDNA-Binding ProteinsDNA Repair EnzymesMRE11 Homologue ProteinMRE11 protein, humanMutant ProteinsNBN protein, humanNuclear ProteinsRAD50 protein, humanSmall Ubiquitin-Related Modifier Proteins

Identifiers

PMID22740413
PMCPMC3446602
OpenAlexW1975609735

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.