Logo des Robert Koch-InstitutLogo des Robert Koch-Institut
Publikationsserver des Robert Koch-Institutsedoc
de|en
Publikation anzeigen 
  • edoc Startseite
  • Artikel in Fachzeitschriften
  • Artikel in Fachzeitschriften
  • Publikation anzeigen
  • edoc Startseite
  • Artikel in Fachzeitschriften
  • Artikel in Fachzeitschriften
  • Publikation anzeigen
JavaScript is disabled for your browser. Some features of this site may not work without it.
Gesamter edoc-ServerBereiche & SammlungenTitelAutorSchlagwortDiese SammlungTitelAutorSchlagwort
PublizierenEinloggenRegistrierenHilfe
StatistikNutzungsstatistik
Gesamter edoc-ServerBereiche & SammlungenTitelAutorSchlagwortDiese SammlungTitelAutorSchlagwort
PublizierenEinloggenRegistrierenHilfe
StatistikNutzungsstatistik
Publikation anzeigen 
  • edoc Startseite
  • Artikel in Fachzeitschriften
  • Artikel in Fachzeitschriften
  • Publikation anzeigen
  • edoc Startseite
  • Artikel in Fachzeitschriften
  • Artikel in Fachzeitschriften
  • Publikation anzeigen
2013-08-08Zeitschriftenartikel DOI: 10.1371/journal.ppat.1003544
Cytomegalovirus Downregulates IRE1 to Repress the Unfolded Protein Response
Stahl, Sebastian
Burkhart, Julia M.
Hinte, Florian
Tirosh, Boaz
Mohr, Hermine
Zahedi, René P.
Sickmann, Albert
Ruzsics, Zsolt
Budt, Matthias
Brune, Wolfram
During viral infection, a massive demand for viral glycoproteins can overwhelm the capacity of the protein folding and quality control machinery, leading to an accumulation of unfolded proteins in the endoplasmic reticulum (ER). To restore ER homeostasis, cells initiate the unfolded protein response (UPR) by activating three ER-to-nucleus signaling pathways, of which the inositol-requiring enzyme 1 (IRE1)-dependent pathway is the most conserved. To reduce ER stress, the UPR decreases protein synthesis, increases degradation of unfolded proteins, and upregulates chaperone expression to enhance protein folding. Cytomegaloviruses, as other viral pathogens, modulate the UPR to their own advantage. However, the molecular mechanisms and the viral proteins responsible for UPR modulation remained to be identified. In this study, we investigated the modulation of IRE1 signaling by murine cytomegalovirus (MCMV) and found that IRE1-mediated mRNA splicing and expression of the X-box binding protein 1 (XBP1) is repressed in infected cells. By affinity purification, we identified the viral M50 protein as an IRE1-interacting protein. M50 expression in transfected or MCMV-infected cells induced a substantial downregulation of IRE1 protein levels. The N-terminal conserved region of M50 was found to be required for interaction with and downregulation of IRE1. Moreover, UL50, the human cytomegalovirus (HCMV) homolog of M50, affected IRE1 in the same way. Thus we concluded that IRE1 downregulation represents a previously undescribed viral strategy to curb the UPR.
Dateien zu dieser Publikation
Thumbnail
226PDID9SO216.pdf — PDF — 6.068 Mb
MD5: 4a3bce9606e96ff27002ffa222129b7f
Zitieren
BibTeX
EndNote
RIS
Keine Lizenzangabe
Zur Langanzeige

Verwandte Publikationen

Anzeige der Publikationen mit ähnlichem Titel, Autor, Urheber und Thema.

  • 2008-11-19Zeitschriftenartikel
    Specific Inhibition of the PKR-Mediated Antiviral Response by the Murine Cytomegalovirus Proteins m142 and m143 
    Budt, Matthias; Niederstadt, Lars; Valchanova, Ralitsa S.; Jonjic, Stipan; Brune, Wolfram
    Double-stranded RNA (dsRNA) produced during viral infection activates several cellular antiviral responses. Among the best characterized is the shutoff of protein synthesis mediated by the dsRNA-dependent protein kinase ...
  • 2012-12-21Zeitschriftenartikel
    Protein-Protein Interaction Domains of Bacillus subtilis DivIVA 
    Baarle, Suey van; Celik, Ilkay Nazli; Kaval, Karan Gautam; Bramkamp, Marc; Hamoen, Leendert W.; Halbedel, Sven
    DivIVA proteins are curvature-sensitive membrane binding proteins that recruit other proteins to the poles and the division septum. They consist of a conserved N-terminal lipid binding domain fused to a less conserved ...
  • 2013-03-11Zeitschriftenartikel
    Towards further reduction and replacement of animal bioassays in prion research by cell and protein misfolding cyclic amplification assays 
    Boerner, Susann; Wagenführ, Katja; Daus, Martin L.; Thomzig, Achim; Beekes, Michael
    Laboratory animals have long since been used extensively in bioassays for prions in order to quantify, usually in terms of median infective doses [ID50], how infectious these pathogens are in vivo. The identification of ...
Nutzungsbedingungen Impressum Leitlinien Datenschutzerklärung Kontakt

Das Robert Koch-Institut ist ein Bundesinstitut im

Geschäftsbereich des Bundesministeriums für Gesundheit

© Robert Koch Institut

Alle Rechte vorbehalten, soweit nicht ausdrücklich anders vermerkt.

 
DOI
10.1371/journal.ppat.1003544
Permanent URL
https://doi.org/10.1371/journal.ppat.1003544
HTML
<a href="https://doi.org/10.1371/journal.ppat.1003544">https://doi.org/10.1371/journal.ppat.1003544</a>