biostudies-literatureUnknown9Nakamura M<h4>Background</h4>Tat-mediated activation of the HIV-1 promoter depends upon a proteasome-associated factor, PAAF1, which dissociates 26S proteasome to produce 19S RP that is essential for transcriptional elongation. The effect of PAAF1 on proteasome activity could also potentially shield certain factors from proteolysis, which may be implicated in the transcriptional co-activator activity of PAAF1 towards the LTR.<h4>Results</h4>Here, we show that Spt6 is targeted by proteasome in the absence of PAAF1. PAAF1 interacts with the N-terminus of Spt6, suggesting that PAAF1 protects Spt6 from proteolysis. Depletion of either PAAF1 or Spt6 reduced histone occupancy at the HIV-1 promoter, and induced the synthesis of aberrant transcripts. Ectopic Spt6 expression or treatment with proteasome inhiRetrovirology13https://www.ebi.ac.uk/biostudies/studies/S-EPMC3305501biostudies-literatureSpt6 levels are modulated by PAAF1 and proteasome to regulate the HIV-1 LTR.PMC3305501Nakamura MKiernan RRousset ELatreille DHenaoui ISLassot IBeraud CMari BBasavarajaiah PfalseSpt6 levels are modulated by PAAF1 and proteasome to regulate the HIV-1 LTR.<h4>Background</h4>Tat-mediated activation of the HIV-1 promoter depends upon a proteasome-associated factor, PAAF1, which dissociates 26S proteasome to produce 19S RP that is essential for transcriptional elongation. The effect of PAAF1 on proteasome activity could also potentially shield certain factors from proteolysis, which may be implicated in the transcriptional co-activator activity of PAAF1 towards the LTR.<h4>Results</h4>Here, we show that Spt6 is targeted by proteasome in the absence of PAAF1. PAAF1 interacts with the N-terminus of Spt6, suggesting that PAAF1 protects Spt6 from proteolysis. Depletion of either PAAF1 or Spt6 reduced histone occupancy at the HIV-1 promoter, and induced the synthesis of aberrant transcripts. Ectopic Spt6 expression or treatment with proteasome inhi2012-01-01T00:00:00Z2012 Feb2026-04-29T03:13:47.532Z2026-04-29T03:08:42.5ZS-EPMC33055012231613810.1186/1742-4690-9-13