Evidence map›Paper›PMID 26786098›Full record

ArticleThe Journal of biological chemistry2016

Identification of Kaposi Sarcoma Herpesvirus (KSHV) vIRF1 Protein as a Novel Interaction Partner of Human Deubiquitinase USP7.

Sara Chavoshi, Olga Egorova, Ira Kay Lacdao, Sahar Farhadi, Yi Sheng, Vivian Saridakis

Open access · hybridAbstract read
In one paragraph

Article in The Journal of biological chemistry, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.

0numbers the graph read from it
0cells of the map it votes in
37citing papers in PubMed
2.5field-weighted citation impact, top 9% 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

37 citing papers in PubMed, 46 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

6 authors at 1 institution in 1 country.

Sara ChavoshiFrom the Department of Biology, York University, Toronto, Ontario M3J 1P3, Canada.
Olga EgorovaFrom the Department of Biology, York University, Toronto, Ontario M3J 1P3, Canada.
Ira Kay LacdaoFrom the Department of Biology, York University, Toronto, Ontario M3J 1P3, Canada.
Sahar FarhadiFrom the Department of Biology, York University, Toronto, Ontario M3J 1P3, Canada.
Yi ShengFrom the Department of Biology, York University, Toronto, Ontario M3J 1P3, Canada.
Vivian SaridakisFrom the Department of Biology, York University, Toronto, Ontario M3J 1P3, Canada vsaridak@yorku.ca.
York University · CA

Funding

Canadian Institutes of Health Research 106583
6 · The paper itself

Abstract

Viral interferon regulatory factor 1 (vIRF1), a Kaposi sarcoma herpesvirus protein, destabilizes p53 by inhibiting p53 acetylation and Hdm2 phosphorylation. This leads to increased ubiquitination and degradation of p53 by Hdm2, which cripples the cellular p53-mediated antiviral response. Ubiquitin-specific protease 7 (USP7) deubiquitinates p53 and Hdm2 and regulates their stability. We identified an EGPS consensus sequence in vIRF1, which is identical to that found in Epstein-Barr virus nuclear antigen 1 (EBNA1) that interacts with the N-terminal domain of USP7 (USP7-NTD). GST pulldown assays demonstrated that vIRF1 interacts with USP7-NTD via its EGPS motif. NMR heteronuclear single quantum correlation (HSQC) analysis revealed chemical perturbations after titration of USP7-NTD with vIRF1 (44)SPGEGPSGTG(53) peptide. In contrast, these perturbations were reduced with a mutant vIRF1 peptide, (44)SPGEGPAGTG(53). Fluorescence polarization analysis indicated that the vIRF1 peptide interacted with USP7-NTD with a Kd of 2.0 μm. The crystal structure of the USP7-NTD·vIRF1 peptide complex revealed an identical mode of binding as that of the EBNA1 peptide to USP7-NTD. We also showed that USP7 interacts with vIRF1 in U2OS cells. Decreased levels of p53, but not Hdm2 or ataxia telangiectasia-mutated (ATM), were seen after expression of vIRF1, but not with a vIRF1 mutant protein. Our results support a new role for vIRF1 through deregulation of the deubiquitinating enzyme USP7 to inhibit p53-mediated antiviral responses.

Indexed as

Herpesvirus 8, HumanAmino Acid MotifsCatalytic DomainCell Line, TumorCrystallography, X-RayHumansInterferon Regulatory FactorsModels, MolecularProtein BindingProtein Interaction Domains and MotifsProtein StabilityTumor Suppressor Protein p53Ubiquitin-Specific Peptidase 7Ubiquitin ThiolesteraseViral ProteinsInterferon Regulatory FactorsTP53 protein, humanTumor Suppressor Protein p53Ubiquitin-Specific Peptidase 7Ubiquitin ThiolesteraseUSP7 protein, humanviral interferon regulatory factorsViral Proteinsdeubiquitylation (deubiquitination)DNA virusesKSHVUSP7viral proteinvIRF1virologyX-ray crystallography

Identifiers

PMID26786098
PMCPMC4813580
OpenAlexW2329841178

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.