Nullbasic, a potent anti-HIV tat mutant, induces CRM1-dependent disruption of HIV rev trafficking.

Nullbasic, a mutant of the HIV-1 Tat protein, has anti-HIV-1 activity through mechanisms that include inhibition of Rev function and redistribution of the HIV-1 Rev protein from the nucleolus to the nucleoplasm and cytoplasm. Here we investigate the mechanism of this effect for the first time, estab...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Min-Hsuan Lin, Haran Sivakumaran, Ann Apolloni, Ting Wei, David A Jans, David Harrich
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2012
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/2b1935cdd4aa4ab88b18f0518e0a6c69
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:2b1935cdd4aa4ab88b18f0518e0a6c69
record_format	dspace
spelling	oai:doaj.org-article:2b1935cdd4aa4ab88b18f0518e0a6c692021-11-18T08:05:43ZNullbasic, a potent anti-HIV tat mutant, induces CRM1-dependent disruption of HIV rev trafficking.1932-620310.1371/journal.pone.0051466https://doaj.org/article/2b1935cdd4aa4ab88b18f0518e0a6c692012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23251541/?tool=EBIhttps://doaj.org/toc/1932-6203Nullbasic, a mutant of the HIV-1 Tat protein, has anti-HIV-1 activity through mechanisms that include inhibition of Rev function and redistribution of the HIV-1 Rev protein from the nucleolus to the nucleoplasm and cytoplasm. Here we investigate the mechanism of this effect for the first time, establishing that redistribution of Rev by Nullbasic is not due to direct interaction between the two proteins. Rather, Nullbasic affects subcellular localization of cellular proteins that regulate Rev trafficking. In particular, Nullbasic induced redistribution of exportin 1 (CRM1), nucleophosmin (B23) and nucleolin (C23) from the nucleolus to the nucleus when Rev was coexpressed, but never in its absence. Inhibition of the Rev:CRM1 interaction by leptomycin B or a non-interacting RevM10 mutant completely blocked redistribution of Rev by Nullbasic. Finally, Nullbasic did not inhibit importin β- or transportin 1-mediated nuclear import, suggesting that cytoplasmic accumulation of Rev was due to increased export by CRM1. Overall, our data support the conclusion that CRM1-dependent subcellular redistribution of Rev from the nucleolus by Nullbasic is not through general perturbation of either nuclear import or export. Rather, Nullbasic appears to interact with and disrupt specific components of a Rev trafficking complex required for its nucleocytoplasmic shuttling and, in particular, its nucleolar accumulation.Min-Hsuan LinHaran SivakumaranAnn ApolloniTing WeiDavid A JansDavid HarrichPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 7, Iss 12, p e51466 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Min-Hsuan Lin Haran Sivakumaran Ann Apolloni Ting Wei David A Jans David Harrich Nullbasic, a potent anti-HIV tat mutant, induces CRM1-dependent disruption of HIV rev trafficking.
description	Nullbasic, a mutant of the HIV-1 Tat protein, has anti-HIV-1 activity through mechanisms that include inhibition of Rev function and redistribution of the HIV-1 Rev protein from the nucleolus to the nucleoplasm and cytoplasm. Here we investigate the mechanism of this effect for the first time, establishing that redistribution of Rev by Nullbasic is not due to direct interaction between the two proteins. Rather, Nullbasic affects subcellular localization of cellular proteins that regulate Rev trafficking. In particular, Nullbasic induced redistribution of exportin 1 (CRM1), nucleophosmin (B23) and nucleolin (C23) from the nucleolus to the nucleus when Rev was coexpressed, but never in its absence. Inhibition of the Rev:CRM1 interaction by leptomycin B or a non-interacting RevM10 mutant completely blocked redistribution of Rev by Nullbasic. Finally, Nullbasic did not inhibit importin β- or transportin 1-mediated nuclear import, suggesting that cytoplasmic accumulation of Rev was due to increased export by CRM1. Overall, our data support the conclusion that CRM1-dependent subcellular redistribution of Rev from the nucleolus by Nullbasic is not through general perturbation of either nuclear import or export. Rather, Nullbasic appears to interact with and disrupt specific components of a Rev trafficking complex required for its nucleocytoplasmic shuttling and, in particular, its nucleolar accumulation.
format	article
author	Min-Hsuan Lin Haran Sivakumaran Ann Apolloni Ting Wei David A Jans David Harrich
author_facet	Min-Hsuan Lin Haran Sivakumaran Ann Apolloni Ting Wei David A Jans David Harrich
author_sort	Min-Hsuan Lin
title	Nullbasic, a potent anti-HIV tat mutant, induces CRM1-dependent disruption of HIV rev trafficking.
title_short	Nullbasic, a potent anti-HIV tat mutant, induces CRM1-dependent disruption of HIV rev trafficking.
title_full	Nullbasic, a potent anti-HIV tat mutant, induces CRM1-dependent disruption of HIV rev trafficking.
title_fullStr	Nullbasic, a potent anti-HIV tat mutant, induces CRM1-dependent disruption of HIV rev trafficking.
title_full_unstemmed	Nullbasic, a potent anti-HIV tat mutant, induces CRM1-dependent disruption of HIV rev trafficking.
title_sort	nullbasic, a potent anti-hiv tat mutant, induces crm1-dependent disruption of hiv rev trafficking.
publisher	Public Library of Science (PLoS)
publishDate	2012
url	https://doaj.org/article/2b1935cdd4aa4ab88b18f0518e0a6c69
work_keys_str_mv	AT minhsuanlin nullbasicapotentantihivtatmutantinducescrm1dependentdisruptionofhivrevtrafficking AT haransivakumaran nullbasicapotentantihivtatmutantinducescrm1dependentdisruptionofhivrevtrafficking AT annapolloni nullbasicapotentantihivtatmutantinducescrm1dependentdisruptionofhivrevtrafficking AT tingwei nullbasicapotentantihivtatmutantinducescrm1dependentdisruptionofhivrevtrafficking AT davidajans nullbasicapotentantihivtatmutantinducescrm1dependentdisruptionofhivrevtrafficking AT davidharrich nullbasicapotentantihivtatmutantinducescrm1dependentdisruptionofhivrevtrafficking
_version_	1718422217816014848

Nullbasic, a potent anti-HIV tat mutant, induces CRM1-dependent disruption of HIV rev trafficking.

Ejemplares similares