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Phosphorylation of Large T Antigen Regulates Merkel Cell Polyomavirus Replication
Merkel Cell Polyomavirus (MCPyV) was recently discovered as a novel human polyomavirus that is associated with ~80% of Merkel Cell Carcinomas. The Large Tumor antigen (LT) is an early viral protein which has a variety of functions, including manipulation of the cell cycle and initiating viral DNA re...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4190550/ https://www.ncbi.nlm.nih.gov/pubmed/25006834 http://dx.doi.org/10.3390/cancers6031464 |
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author | Diaz, Jason Wang, Xin Tsang, Sabrina H. Jiao, Jing You, Jianxin |
author_facet | Diaz, Jason Wang, Xin Tsang, Sabrina H. Jiao, Jing You, Jianxin |
author_sort | Diaz, Jason |
collection | PubMed |
description | Merkel Cell Polyomavirus (MCPyV) was recently discovered as a novel human polyomavirus that is associated with ~80% of Merkel Cell Carcinomas. The Large Tumor antigen (LT) is an early viral protein which has a variety of functions, including manipulation of the cell cycle and initiating viral DNA replication. Phosphorylation plays a critical regulatory role for polyomavirus LT proteins, but no investigation of MCPyV LT phosphorylation has been performed to date. In this report mass spectrometry analysis reveals three unique phosphorylation sites: T271, T297 and T299. In vivo replication assays confirm that phosphorylation of T271 does not play a role in viral replication, while modification at T297 and T299 have dramatic and opposing effects on LT’s ability to initiate replication from the viral origin. We test these mutants for their ability to bind, unwind, and act as a functional helicase at the viral origin. These studies provide a framework for understanding how phosphorylation of LT may dynamically regulate viral replication. Although the natural host cell of MCPyV has not yet been established, this work provides a foundation for understanding how LT activity is regulated and provides tools for better exploring this regulation in both natural host cells and Merkel cells. |
format | Online Article Text |
id | pubmed-4190550 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-41905502014-10-09 Phosphorylation of Large T Antigen Regulates Merkel Cell Polyomavirus Replication Diaz, Jason Wang, Xin Tsang, Sabrina H. Jiao, Jing You, Jianxin Cancers (Basel) Article Merkel Cell Polyomavirus (MCPyV) was recently discovered as a novel human polyomavirus that is associated with ~80% of Merkel Cell Carcinomas. The Large Tumor antigen (LT) is an early viral protein which has a variety of functions, including manipulation of the cell cycle and initiating viral DNA replication. Phosphorylation plays a critical regulatory role for polyomavirus LT proteins, but no investigation of MCPyV LT phosphorylation has been performed to date. In this report mass spectrometry analysis reveals three unique phosphorylation sites: T271, T297 and T299. In vivo replication assays confirm that phosphorylation of T271 does not play a role in viral replication, while modification at T297 and T299 have dramatic and opposing effects on LT’s ability to initiate replication from the viral origin. We test these mutants for their ability to bind, unwind, and act as a functional helicase at the viral origin. These studies provide a framework for understanding how phosphorylation of LT may dynamically regulate viral replication. Although the natural host cell of MCPyV has not yet been established, this work provides a foundation for understanding how LT activity is regulated and provides tools for better exploring this regulation in both natural host cells and Merkel cells. MDPI 2014-07-08 /pmc/articles/PMC4190550/ /pubmed/25006834 http://dx.doi.org/10.3390/cancers6031464 Text en © 2014 by the authors; licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution license (http://creativecommons.org/licenses/by/3.0/). |
spellingShingle | Article Diaz, Jason Wang, Xin Tsang, Sabrina H. Jiao, Jing You, Jianxin Phosphorylation of Large T Antigen Regulates Merkel Cell Polyomavirus Replication |
title | Phosphorylation of Large T Antigen Regulates Merkel Cell Polyomavirus Replication |
title_full | Phosphorylation of Large T Antigen Regulates Merkel Cell Polyomavirus Replication |
title_fullStr | Phosphorylation of Large T Antigen Regulates Merkel Cell Polyomavirus Replication |
title_full_unstemmed | Phosphorylation of Large T Antigen Regulates Merkel Cell Polyomavirus Replication |
title_short | Phosphorylation of Large T Antigen Regulates Merkel Cell Polyomavirus Replication |
title_sort | phosphorylation of large t antigen regulates merkel cell polyomavirus replication |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4190550/ https://www.ncbi.nlm.nih.gov/pubmed/25006834 http://dx.doi.org/10.3390/cancers6031464 |
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