Evidence map›Paper›PMID 25782006›Full record

ArticlePLoS pathogens2015

Evidence for ubiquitin-regulated nuclear and subnuclear trafficking among Paramyxovirinae matrix proteins.

Mickey Pentecost, Ajay A Vashisht, Talia Lester, Tim Voros, Shannon M Beaty, Arnold Park, Yao E Wang, Tatyana E Yun, Alexander N Freiberg, James A Wohlschlegel and 1 more

Open access · goldAbstract read
In one paragraph

Article in PLoS pathogens, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 59 papers.

0numbers the graph read from it
0cells of the map it votes in
59citing papers in PubMed
5.7field-weighted citation impact, top 3% 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

59 citing papers in PubMed, 86 citations in OpenAlex.

  1. Article
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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.

Mickey PentecostDepartment of Microbiology, Immunology, and Molecular Genetics, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California, United States of America.
Ajay A VashishtDepartment of Biological Chemistry, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California, United States of America.
Talia LesterDepartment of Microbiology, Immunology, and Molecular Genetics, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California, United States of America.
Tim VorosDepartment of Microbiology, Immunology, and Molecular Genetics, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California, United States of America.
Shannon M BeatyDepartment of Microbiology, Icahn School of Medicine at Mount Sinai, New York, New York, United States of America.
Arnold ParkDepartment of Microbiology, Immunology, and Molecular Genetics, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California, United States of America.
Yao E WangDepartment of Microbiology, Immunology, and Molecular Genetics, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California, United States of America.
Tatyana E YunDepartment of Pathology, University of Texas Medical Branch, Galveston, Texas, United States of America.
Alexander N FreibergDepartment of Pathology, University of Texas Medical Branch, Galveston, Texas, United States of America.
James A WohlschlegelDepartment of Biological Chemistry, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California, United States of America.
Benhur LeeDepartment of Microbiology, Immunology, and Molecular Genetics, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California, United States of America; Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, New York, United States of America.
University of California, Los Angeles · USIcahn School of Medicine at Mount Sinai · USThe University of Texas Medical Branch at Galveston · US

Funding

Vaccines and Diagnostics TrialsU54AI065359 · NIAID · UNIVERSITY OF CALIFORNIA-IRVINE · PI BARBOUR, ALAN G. · 2005 to 2013
$88.8M
UCLA NIGMS T32 Program AssessmentT32GM007185 · NIGMS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI TORRES, JORGE · 1985 to 2020
$21.7M
MULTIDISCIPLINARY TRAINING IN MICROBIAL PATHOGENESIST32AI007323 · NIAID · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI Peter John Bradley · 1988 to 2026
$8.6M
Proteolytic Control of Iron Metabolism by the Ubiquitin Ligase FBXL5R01GM089778 · NIGMS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI WOHLSCHLEGEL, JAMES AKIRA · 2010 to 2023
$4.0M
Interdisciplinary Training in Virology and Gene TherapyT32AI060567 · NIAID · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI WU, TING-TING · 2004 to 2018
$3.4M
Envelope-receptor interactions in Nipah and Hendra virus pathobiologyR01AI069317 · NIAID · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI LEE, BENHUR · 2007 to 2011
$1.7M
Bioavailable proteasome inhibitors as broad-spectrum antiviralsR33AI102267 · NIAID · UNIVERSITY OF TEXAS MED BR GALVESTON · PI FREIBERG, ALEXANDER NICLAS · 2014 to 2016
$1.2M
Bioavailable proteasome inhibitors as broad-spectrum antiviralsR21AI102267 · NIAID · UNIVERSITY OF TEXAS MED BR GALVESTON · PI FREIBERG, ALEXANDER NICLAS · 2012 to 2013
$360k
SUMO and ubiquitin modifications in Nipah virus matrix trafficking and functionF32AI100498 · NIAID · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI PENTECOST, MICKEY JOSEPH · 2013 to 2014
$111k
NIAID NIH HHS F32 AI100498NIAID NIH HHS R01 AI069317NIAID NIH HHS R21 AI102267NIAID NIH HHS R33 AI102267NIAID NIH HHS T32 AI007323NIAID NIH HHS T32 AI060567NIAID NIH HHS T32 AI07323NIAID NIH HHS U54 AI065359NIGMS NIH HHS GM089778NIGMS NIH HHS R01 GM089778NIGMS NIH HHS T32 GM007185
6 · The paper itself

Abstract

The paramyxovirus matrix (M) protein is a molecular scaffold required for viral morphogenesis and budding at the plasma membrane. Transient nuclear residence of some M proteins hints at non-structural roles. However, little is known regarding the mechanisms that regulate the nuclear sojourn. Previously, we found that the nuclear-cytoplasmic trafficking of Nipah virus M (NiV-M) is a prerequisite for budding, and is regulated by a bipartite nuclear localization signal (NLSbp), a leucine-rich nuclear export signal (NES), and monoubiquitination of the K258 residue within the NLSbp itself (NLSbp-lysine). To define whether the sequence determinants of nuclear trafficking identified in NiV-M are common among other Paramyxovirinae M proteins, we generated the homologous NES and NLSbp-lysine mutations in M proteins from the five major Paramyxovirinae genera. Using quantitative 3D confocal microscopy, we determined that the NES and NLSbp-lysine are required for the efficient nuclear export of the M proteins of Nipah virus, Hendra virus, Sendai virus, and Mumps virus. Pharmacological depletion of free ubiquitin or mutation of the conserved NLSbp-lysine to an arginine, which inhibits M ubiquitination, also results in nuclear and nucleolar retention of these M proteins. Recombinant Sendai virus (rSeV-eGFP) bearing the NES or NLSbp-lysine M mutants rescued at similar efficiencies to wild type. However, foci of cells expressing the M mutants displayed marked fusogenicity in contrast to wild type, and infection did not spread. Recombinant Mumps virus (rMuV-eGFP) bearing the homologous mutations showed similar defects in viral morphogenesis. Finally, shotgun proteomics experiments indicated that the interactomes of Paramyxovirinae M proteins are significantly enriched for components of the nuclear pore complex, nuclear transport receptors, and nucleolar proteins. We then synthesize our functional and proteomics data to propose a working model for the ubiquitin-regulated nuclear-cytoplasmic trafficking of cognate paramyxovirus M proteins that show a consistent nuclear trafficking phenotype.

Indexed as

Amino Acid SequenceAnimalsCell NucleusChlorocebus aethiopsHeLa CellsHumansImaging, Three-DimensionalImmunoblottingImmunoprecipitationMicroscopy, ConfocalNuclear Localization SignalsParamyxovirinaeProtein TransportTransfectionUbiquitinVero CellsNuclear Localization SignalsUbiquitinViral Matrix Proteins

Identifiers

PMID25782006
PMCPMC4363627
OpenAlexW2018890449

What OpenQuestion holds

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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.