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A Ubiquitin-specific Protease Possesses a Decisive Role for Adenovirus Replication and Oncogene-mediated Transformation

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 regul...

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Autores principales: Ching, Wilhelm, Koyuncu, Emre, Singh, Sonia, Arbelo-Roman, Christina, Hartl, Barbara, Kremmer, Elisabeth, Speiseder, Thomas, Meier, Chris, Dobner, Thomas
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3610741/
https://www.ncbi.nlm.nih.gov/pubmed/23555268
http://dx.doi.org/10.1371/journal.ppat.1003273
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author Ching, Wilhelm
Koyuncu, Emre
Singh, Sonia
Arbelo-Roman, Christina
Hartl, Barbara
Kremmer, Elisabeth
Speiseder, Thomas
Meier, Chris
Dobner, Thomas
author_facet Ching, Wilhelm
Koyuncu, Emre
Singh, Sonia
Arbelo-Roman, Christina
Hartl, Barbara
Kremmer, Elisabeth
Speiseder, Thomas
Meier, Chris
Dobner, Thomas
author_sort Ching, Wilhelm
collection PubMed
description 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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spelling pubmed-36107412013-04-03 A Ubiquitin-specific Protease Possesses a Decisive Role for Adenovirus Replication and Oncogene-mediated Transformation Ching, Wilhelm Koyuncu, Emre Singh, Sonia Arbelo-Roman, Christina Hartl, Barbara Kremmer, Elisabeth Speiseder, Thomas Meier, Chris Dobner, Thomas PLoS Pathog Research Article 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. Public Library of Science 2013-03-28 /pmc/articles/PMC3610741/ /pubmed/23555268 http://dx.doi.org/10.1371/journal.ppat.1003273 Text en © 2013 Ching et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Ching, Wilhelm
Koyuncu, Emre
Singh, Sonia
Arbelo-Roman, Christina
Hartl, Barbara
Kremmer, Elisabeth
Speiseder, Thomas
Meier, Chris
Dobner, Thomas
A Ubiquitin-specific Protease Possesses a Decisive Role for Adenovirus Replication and Oncogene-mediated Transformation
title A Ubiquitin-specific Protease Possesses a Decisive Role for Adenovirus Replication and Oncogene-mediated Transformation
title_full A Ubiquitin-specific Protease Possesses a Decisive Role for Adenovirus Replication and Oncogene-mediated Transformation
title_fullStr A Ubiquitin-specific Protease Possesses a Decisive Role for Adenovirus Replication and Oncogene-mediated Transformation
title_full_unstemmed A Ubiquitin-specific Protease Possesses a Decisive Role for Adenovirus Replication and Oncogene-mediated Transformation
title_short A Ubiquitin-specific Protease Possesses a Decisive Role for Adenovirus Replication and Oncogene-mediated Transformation
title_sort ubiquitin-specific protease possesses a decisive role for adenovirus replication and oncogene-mediated transformation
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3610741/
https://www.ncbi.nlm.nih.gov/pubmed/23555268
http://dx.doi.org/10.1371/journal.ppat.1003273
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