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Interplay of Rad51 with NF-κB Pathway Stimulates Expression of HIV-1

Transcription from the HIV-1 promoter is controlled by a series of ubiquitous and inducible cellular proteins with the ability to enter the nucleus and interact with the promoter. A DNA sequence spanning nucleotides −120 to −80, which supports the association of the inducible NF-κB transcription fac...

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Autores principales: Kaminski, Rafal, Wollebo, Hassen S., Datta, Prasun K., White, Martyn K., Amini, Shohreh, Khalili, Kamel
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4029908/
https://www.ncbi.nlm.nih.gov/pubmed/24847939
http://dx.doi.org/10.1371/journal.pone.0098304
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author Kaminski, Rafal
Wollebo, Hassen S.
Datta, Prasun K.
White, Martyn K.
Amini, Shohreh
Khalili, Kamel
author_facet Kaminski, Rafal
Wollebo, Hassen S.
Datta, Prasun K.
White, Martyn K.
Amini, Shohreh
Khalili, Kamel
author_sort Kaminski, Rafal
collection PubMed
description Transcription from the HIV-1 promoter is controlled by a series of ubiquitous and inducible cellular proteins with the ability to enter the nucleus and interact with the promoter. A DNA sequence spanning nucleotides −120 to −80, which supports the association of the inducible NF-κB transcription factor, has received much attention. Here we demonstrate that the interplay between Rad51, a key regulator of the homologous recombination pathway of DNA repair and whose level is induced upon HIV-1 infection, with the NF-κB pathway, augments transcription of the viral promoter. Evidently, stimulation of the NF-κB pathway by PMA and/or TSA promotes association of Rad51 with the LTR DNA sequence and that the p65 subunit of NF-κB is important for this event. Our results also demonstrate that, similar to p65, Rad51 utilizes the NF-κB pathway to position itself in the nucleus as ectopic expression of an IκB mutant impedes its nuclear appearance and transcriptional activity upon the HIV-1 LTR. Treatment of peripheral blood mononuclear cells with small molecules that inhibit Rad51 activity results in greater than 50% decrease in the HIV-1 infection of cells. These observations provide evidence for the involvement of DNA repair factors in control of HIV-1 gene activation and offer a new avenue for the development of anti-viral therapeutics that affect viral gene transcription in latently infected cells.
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spelling pubmed-40299082014-05-28 Interplay of Rad51 with NF-κB Pathway Stimulates Expression of HIV-1 Kaminski, Rafal Wollebo, Hassen S. Datta, Prasun K. White, Martyn K. Amini, Shohreh Khalili, Kamel PLoS One Research Article Transcription from the HIV-1 promoter is controlled by a series of ubiquitous and inducible cellular proteins with the ability to enter the nucleus and interact with the promoter. A DNA sequence spanning nucleotides −120 to −80, which supports the association of the inducible NF-κB transcription factor, has received much attention. Here we demonstrate that the interplay between Rad51, a key regulator of the homologous recombination pathway of DNA repair and whose level is induced upon HIV-1 infection, with the NF-κB pathway, augments transcription of the viral promoter. Evidently, stimulation of the NF-κB pathway by PMA and/or TSA promotes association of Rad51 with the LTR DNA sequence and that the p65 subunit of NF-κB is important for this event. Our results also demonstrate that, similar to p65, Rad51 utilizes the NF-κB pathway to position itself in the nucleus as ectopic expression of an IκB mutant impedes its nuclear appearance and transcriptional activity upon the HIV-1 LTR. Treatment of peripheral blood mononuclear cells with small molecules that inhibit Rad51 activity results in greater than 50% decrease in the HIV-1 infection of cells. These observations provide evidence for the involvement of DNA repair factors in control of HIV-1 gene activation and offer a new avenue for the development of anti-viral therapeutics that affect viral gene transcription in latently infected cells. Public Library of Science 2014-05-21 /pmc/articles/PMC4029908/ /pubmed/24847939 http://dx.doi.org/10.1371/journal.pone.0098304 Text en © 2014 Kaminski 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
Kaminski, Rafal
Wollebo, Hassen S.
Datta, Prasun K.
White, Martyn K.
Amini, Shohreh
Khalili, Kamel
Interplay of Rad51 with NF-κB Pathway Stimulates Expression of HIV-1
title Interplay of Rad51 with NF-κB Pathway Stimulates Expression of HIV-1
title_full Interplay of Rad51 with NF-κB Pathway Stimulates Expression of HIV-1
title_fullStr Interplay of Rad51 with NF-κB Pathway Stimulates Expression of HIV-1
title_full_unstemmed Interplay of Rad51 with NF-κB Pathway Stimulates Expression of HIV-1
title_short Interplay of Rad51 with NF-κB Pathway Stimulates Expression of HIV-1
title_sort interplay of rad51 with nf-κb pathway stimulates expression of hiv-1
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4029908/
https://www.ncbi.nlm.nih.gov/pubmed/24847939
http://dx.doi.org/10.1371/journal.pone.0098304
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