Interplay of Rad51 with NF-κB pathway stimulates expression of HIV-1.

Interplay of Rad51 with NF-κB pathway stimulates expression of HIV-1.
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DOI:
10.1371/journal.pone.0098304
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发表时间:
2014
期刊:
影响因子:
3.7
通讯作者:
Khalili K
Khalili K
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Kaminski R;Wollebo HS;Datta PK;White MK;Amini S;Khalili K

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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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