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Nuclear targeting of the betanodavirus B1 protein via two arginine-rich domains induces G1/S cell cycle arrest mediated by upregulation of p53/p21

The molecular functions of betanodavirus non-structural protein B and its role in host cell survival remain unclear. In the present study, we examined the roles of specific nuclear targeting domains in B1 localization as well as the effect of B1 nuclear localization on the cell cycle and host cell s...

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Autores principales: Su, Yu-Chin, Reshi, Latif, Chen, Lei-Jia, Li, Wei-Han, Chiu, Hsuan-Wen, Hong, Jiann-Ruey
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5814437/
https://www.ncbi.nlm.nih.gov/pubmed/29449573
http://dx.doi.org/10.1038/s41598-018-21340-x
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author Su, Yu-Chin
Reshi, Latif
Chen, Lei-Jia
Li, Wei-Han
Chiu, Hsuan-Wen
Hong, Jiann-Ruey
author_facet Su, Yu-Chin
Reshi, Latif
Chen, Lei-Jia
Li, Wei-Han
Chiu, Hsuan-Wen
Hong, Jiann-Ruey
author_sort Su, Yu-Chin
collection PubMed
description The molecular functions of betanodavirus non-structural protein B and its role in host cell survival remain unclear. In the present study, we examined the roles of specific nuclear targeting domains in B1 localization as well as the effect of B1 nuclear localization on the cell cycle and host cell survival. The B1 protein of the Red spotted grouper nervous necrosis virus (RGNNV) was detected in GF-1 grouper cells as early as 24 hours post-infection (hpi). Using an EYFP-B1 fusion construct, we observed nuclear localization of the B1 protein (up to 99%) in GF-1 cells at 48 hpi. The nuclear localization of B1 was mediated by two arginine-rich nuclear targeting domains (B domain: (46)RRSRR(51); C domain: (63)RDKRPRR(70)) and domain C was more important than domain B in this process. B1 nuclear localization correlated with upregulation of p53 and p21((wef1/cip1)); downregulation of Cyclin D1, CDK4 and Mdm2; and G1/S cell cycle arrest in GF-1 cells. In conclusion, nuclear targeting of the RGNNV B1 protein via two targeting domains causes cell cycle arrest by up-regulating p53/p21 and down-regulating Mdm2, thereby regulating host cell survival.
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spelling pubmed-58144372018-02-21 Nuclear targeting of the betanodavirus B1 protein via two arginine-rich domains induces G1/S cell cycle arrest mediated by upregulation of p53/p21 Su, Yu-Chin Reshi, Latif Chen, Lei-Jia Li, Wei-Han Chiu, Hsuan-Wen Hong, Jiann-Ruey Sci Rep Article The molecular functions of betanodavirus non-structural protein B and its role in host cell survival remain unclear. In the present study, we examined the roles of specific nuclear targeting domains in B1 localization as well as the effect of B1 nuclear localization on the cell cycle and host cell survival. The B1 protein of the Red spotted grouper nervous necrosis virus (RGNNV) was detected in GF-1 grouper cells as early as 24 hours post-infection (hpi). Using an EYFP-B1 fusion construct, we observed nuclear localization of the B1 protein (up to 99%) in GF-1 cells at 48 hpi. The nuclear localization of B1 was mediated by two arginine-rich nuclear targeting domains (B domain: (46)RRSRR(51); C domain: (63)RDKRPRR(70)) and domain C was more important than domain B in this process. B1 nuclear localization correlated with upregulation of p53 and p21((wef1/cip1)); downregulation of Cyclin D1, CDK4 and Mdm2; and G1/S cell cycle arrest in GF-1 cells. In conclusion, nuclear targeting of the RGNNV B1 protein via two targeting domains causes cell cycle arrest by up-regulating p53/p21 and down-regulating Mdm2, thereby regulating host cell survival. Nature Publishing Group UK 2018-02-15 /pmc/articles/PMC5814437/ /pubmed/29449573 http://dx.doi.org/10.1038/s41598-018-21340-x Text en © The Author(s) 2018 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Su, Yu-Chin
Reshi, Latif
Chen, Lei-Jia
Li, Wei-Han
Chiu, Hsuan-Wen
Hong, Jiann-Ruey
Nuclear targeting of the betanodavirus B1 protein via two arginine-rich domains induces G1/S cell cycle arrest mediated by upregulation of p53/p21
title Nuclear targeting of the betanodavirus B1 protein via two arginine-rich domains induces G1/S cell cycle arrest mediated by upregulation of p53/p21
title_full Nuclear targeting of the betanodavirus B1 protein via two arginine-rich domains induces G1/S cell cycle arrest mediated by upregulation of p53/p21
title_fullStr Nuclear targeting of the betanodavirus B1 protein via two arginine-rich domains induces G1/S cell cycle arrest mediated by upregulation of p53/p21
title_full_unstemmed Nuclear targeting of the betanodavirus B1 protein via two arginine-rich domains induces G1/S cell cycle arrest mediated by upregulation of p53/p21
title_short Nuclear targeting of the betanodavirus B1 protein via two arginine-rich domains induces G1/S cell cycle arrest mediated by upregulation of p53/p21
title_sort nuclear targeting of the betanodavirus b1 protein via two arginine-rich domains induces g1/s cell cycle arrest mediated by upregulation of p53/p21
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5814437/
https://www.ncbi.nlm.nih.gov/pubmed/29449573
http://dx.doi.org/10.1038/s41598-018-21340-x
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