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KSHV Reactivation and Novel Implications of Protein Isomerization on Lytic Switch Control
In Kaposi’s sarcoma-associated herpesvirus (KSHV) oncogenesis, both latency and reactivation are hypothesized to potentiate tumor growth. The KSHV Rta protein is the lytic switch for reactivation. Rta transactivates essential genes via interactions with cofactors such as the cellular RBP-Jk and Oct-...
Autores principales: | , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4306829/ https://www.ncbi.nlm.nih.gov/pubmed/25588053 http://dx.doi.org/10.3390/v7010072 |
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author | Guito, Jonathan Lukac, David M. |
author_facet | Guito, Jonathan Lukac, David M. |
author_sort | Guito, Jonathan |
collection | PubMed |
description | In Kaposi’s sarcoma-associated herpesvirus (KSHV) oncogenesis, both latency and reactivation are hypothesized to potentiate tumor growth. The KSHV Rta protein is the lytic switch for reactivation. Rta transactivates essential genes via interactions with cofactors such as the cellular RBP-Jk and Oct-1 proteins, and the viral Mta protein. Given that robust viral reactivation would facilitate antiviral responses and culminate in host cell lysis, regulation of Rta’s expression and function is a major determinant of the latent-lytic balance and the fate of infected cells. Our lab recently showed that Rta transactivation requires the cellular peptidyl-prolyl cis/trans isomerase Pin1. Our data suggest that proline‑directed phosphorylation regulates Rta by licensing binding to Pin1. Despite Pin1’s ability to stimulate Rta transactivation, unchecked Pin1 activity inhibited virus production. Dysregulation of Pin1 is implicated in human cancers, and KSHV is the latest virus known to co-opt Pin1 function. We propose that Pin1 is a molecular timer that can regulate the balance between viral lytic gene expression and host cell lysis. Intriguing scenarios for Pin1’s underlying activities, and the potential broader significance for isomerization of Rta and reactivation, are highlighted. |
format | Online Article Text |
id | pubmed-4306829 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-43068292015-02-02 KSHV Reactivation and Novel Implications of Protein Isomerization on Lytic Switch Control Guito, Jonathan Lukac, David M. Viruses Review In Kaposi’s sarcoma-associated herpesvirus (KSHV) oncogenesis, both latency and reactivation are hypothesized to potentiate tumor growth. The KSHV Rta protein is the lytic switch for reactivation. Rta transactivates essential genes via interactions with cofactors such as the cellular RBP-Jk and Oct-1 proteins, and the viral Mta protein. Given that robust viral reactivation would facilitate antiviral responses and culminate in host cell lysis, regulation of Rta’s expression and function is a major determinant of the latent-lytic balance and the fate of infected cells. Our lab recently showed that Rta transactivation requires the cellular peptidyl-prolyl cis/trans isomerase Pin1. Our data suggest that proline‑directed phosphorylation regulates Rta by licensing binding to Pin1. Despite Pin1’s ability to stimulate Rta transactivation, unchecked Pin1 activity inhibited virus production. Dysregulation of Pin1 is implicated in human cancers, and KSHV is the latest virus known to co-opt Pin1 function. We propose that Pin1 is a molecular timer that can regulate the balance between viral lytic gene expression and host cell lysis. Intriguing scenarios for Pin1’s underlying activities, and the potential broader significance for isomerization of Rta and reactivation, are highlighted. MDPI 2015-01-12 /pmc/articles/PMC4306829/ /pubmed/25588053 http://dx.doi.org/10.3390/v7010072 Text en © 2015 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/4.0/). |
spellingShingle | Review Guito, Jonathan Lukac, David M. KSHV Reactivation and Novel Implications of Protein Isomerization on Lytic Switch Control |
title | KSHV Reactivation and Novel Implications of Protein Isomerization on Lytic Switch Control |
title_full | KSHV Reactivation and Novel Implications of Protein Isomerization on Lytic Switch Control |
title_fullStr | KSHV Reactivation and Novel Implications of Protein Isomerization on Lytic Switch Control |
title_full_unstemmed | KSHV Reactivation and Novel Implications of Protein Isomerization on Lytic Switch Control |
title_short | KSHV Reactivation and Novel Implications of Protein Isomerization on Lytic Switch Control |
title_sort | kshv reactivation and novel implications of protein isomerization on lytic switch control |
topic | Review |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4306829/ https://www.ncbi.nlm.nih.gov/pubmed/25588053 http://dx.doi.org/10.3390/v7010072 |
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