Evidence map›Paper›PMID 18321963›Full record

ArticleJournal of virology2008

Human cytomegalovirus UL97 kinase activity is required for the hyperphosphorylation of retinoblastoma protein and inhibits the formation of nuclear aggresomes.

Mark N Prichard, Elizabeth Sztul, Shannon L Daily, Amie L Perry, Samuel L Frederick, Rachel B Gill, Caroll B Hartline, Daniel N Streblow, Susan M Varnum, Richard D Smith and 1 more

Open access · greenAbstract read
In one paragraph

Article in Journal of virology, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 81 papers.

0numbers the graph read from it
0cells of the map it votes in
81citing papers in PubMed
8.6field-weighted citation impact, top 2% 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

81 citing papers in PubMed, 106 citations in OpenAlex.

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  16. Expanding the Known Functional Repertoire of the Human Cytomegalovirus pp71 Protein.Frontiers in cellular and infection microbiology · 2020
    Review
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21 more citing papers are in PubMed but not listed here.

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.

Mark N PrichardDepartment of Pediatrics, University of Alabama School of Medicine, Birmingham, Alabama 35233, USA. mprichard@peds.uab.edu
Elizabeth Sztul
Shannon L Daily
Amie L Perry
Samuel L Frederick
Rachel B Gill
Caroll B Hartline
Daniel N Streblow
Susan M Varnum
Richard D Smith
Earl R Kern
Pacific Northwest National Laboratory · USUniversity of Alabama · USOregon Health & Science University · US

Funding

WORKSHOP AND TRAINING ACTIVITIESP41RR018522 · NCRR · BATTELLE PACIFIC NORTHWEST LABORATORIES · PI SMITH, RICHARD D · 2003 to 2011
$25.1M
Mechanisms of CMV latency in accelerated vascular diseaseR01HL083194 · NHLBI · OREGON HEALTH & SCIENCE UNIVERSITY · PI STREBLOW, DANIEL N · 2006 to 2010
$1.5M
DYNAMICS AND NUCLEAR EFFECTS OF NON-POLYQ AGGREGATESR21NS051422 · NINDS · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI SZTUL, ELIZABETH S · 2005 to 2006
$363k
NCRR NIH HHS P41 RR018522NCRR NIH HHS RR18522NHLBI NIH HHS HL083194NHLBI NIH HHS R01 HL083194NIAID NIH HHS N01 AI030049NIAID NIH HHS N01-AI-30049NINDS NIH HHS NS51422NINDS NIH HHS R21 NS051422
6 · The paper itself

Abstract

Cells infected with human cytomegalovirus in the absence of UL97 kinase activity produce large nuclear aggregates that sequester considerable quantities of viral proteins. A transient expression assay suggested that pp71 and IE1 were also involved in this process, and this suggestion was significant, since both proteins have been reported to interact with components of promyelocytic leukemia (PML) bodies (ND10) and also interact functionally with retinoblastoma pocket proteins (RB). PML bodies have been linked to the formation of nuclear aggresomes, and colocalization studies suggested that viral proteins were recruited to these structures and that UL97 kinase activity inhibited their formation. Proteins associated with PML bodies were examined by Western blot analysis, and pUL97 appeared to specifically affect the phosphorylation of RB in a kinase-dependent manner. Three consensus RB binding motifs were identified in the UL97 kinase, and recombinant viruses were constructed in which each was mutated to assess a potential role in the phosphorylation of RB and the inhibition of nuclear aggresome formation. The mutation of either the conserved LxCxE RB binding motif or the lysine required for kinase activity impaired the ability of the virus to stabilize and phosphorylate RB. We concluded from these studies that both UL97 kinase activity and the LxCxE RB binding motif are required for the phosphorylation and stabilization of RB in infected cells and that this effect can be antagonized by the antiviral drug maribavir. These data also suggest a potential link between RB function and the formation of aggresomes.

Indexed as

Amino Acid SequenceAnimalsBinding SitesCell LineCell NucleusChlorocebus aethiopsChromatography, LiquidConserved SequenceCytomegalovirusCytoplasmHumansMass SpectrometryMicroscopy, FluorescenceMolecular Sequence DataPhosphorylationPhosphotransferases (Alcohol Group Acceptor)ganciclovir kinasePhosphotransferases (Alcohol Group Acceptor)ProteinsRetinoblastoma Protein

Identifiers

PMID18321963
PMCPMC2346732
OpenAlexW2125951714

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.