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Ching, W.* ; Koyuncu, E.* ; Singh, S.* ; Arbelo-Roman, C.* ; Härtl, B.* ; Kremmer, E. ; Speiseder, T.* ; Meier, C.* ; Dobner, T.*

A ubiquitin-specific protease possesses a decisive role for adenovirus replication and oncogene-mediated transformation.

PLoS Pathog. 9:e1003273 (2013)
Verlagsversion Volltext DOI PMC
Open Access Gold
Creative Commons Lizenzvertrag
Adenoviral replication depends on viral as well as cellular proteins. However, little is known about cellular proteins promoting adenoviral replication. In our screens to identify such proteins, we discovered a cellular component of the ubiquitin proteasome pathway interacting with the central regulator of adenoviral replication. Our binding assays mapped a specific interaction between the N-terminal domains of both viral E1B-55K and USP7, a deubiquitinating enzyme. RNA interference-mediated downregulation of USP7 severely reduced E1B-55K protein levels, but more importantly negatively affected adenoviral replication. We also succeeded in resynthesizing an inhibitor of USP7, which like the knockdown background reduced adenoviral replication. Further assays revealed that not only adenoviral growth, but also adenoviral oncogene-driven cellular transformation relies on the functions of USP7. Our data provide insights into an intricate mechanistic pathway usurped by an adenovirus to promote its replication and oncogenic functions, and at the same time open up possibilities for new antiviral strategies.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Korrespondenzautor
Schlagwörter E1b 55-kilodalton Protein ; Small-molecule Inhibitor ; Late Gene-expression ; Dna-replication ; Bioinformatics Analysis ; Tumor-suppressor ; Messenger-rna ; Wild-type ; P53 ; Degradation
ISSN (print) / ISBN 1553-7366
e-ISSN 1553-7374
Zeitschrift PLoS Pathogens
Quellenangaben Band: 9, Heft: 3, Seiten: , Artikelnummer: e1003273 Supplement: ,
Verlag Public Library of Science (PLoS)
Nichtpatentliteratur Publikationen
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Molecular Immunology (IMI)