ArticleRetrovirology2012
Spt6 levels are modulated by PAAF1 and proteasome to regulate the HIV-1 LTR.
Article in Retrovirology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 16 citations in OpenAlex.
- Neuregulin (NRG-1β) Is Pro-Myogenic and Anti-Cachectic in Respiratory Muscles of Post-Myocardial Infarcted Swine.Biology · 2022Article
- Epigenetic Mechanisms of HIV-1 Persistence.Vaccines · 2021Review
- SARS-CoV-2 infection remodels the host protein thermal stability landscape.Molecular systems biology · 2021Article
- SPT6-driven error-free DNA repair safeguards genomic stability of glioblastoma cancer stem-like cells.Nature communications · 2020Article
- Deregulated Expression of Mammalian lncRNA through Loss of SPT6 Induces R-Loop Formation, Replication Stress, and Cellular Senescence.Molecular cell · 2018Article
- Nuclear RNA surveillance complexes silence HIV-1 transcription.PLoS pathogens · 2018Article
- Spt6 Is Essential for rRNA Synthesis by RNA Polymerase I.Molecular and cellular biology · 2015Article
- Spt6 regulates intragenic and antisense transcription, nucleosome positioning, and histone modifications genome-wide in fission yeast.Molecular and cellular biology · 2013Article
- Proteasome inhibitors act as bifunctional antagonists of human immunodeficiency virus type 1 latency and replication.Retrovirology · 2013Article
- Role of cellular iron and oxygen in the regulation of HIV-1 infection.Future virology · 2013Article
- CDK2 regulates HIV-1 transcription by phosphorylation of CDK9 on serine 90.Retrovirology · 2012Article
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Corrections and comments
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundTat-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.
resultsHere, 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 inhibitor partially rescued the transcription defect associated with loss of PAAF1. Transcriptional profiling followed by ChIP identified a subset of cellular genes that are regulated in a similar fashion to HIV-1 by Spt6 and/or PAAF1, including many that are involved in cancer, such as BRCA1 and BARD1.
conclusionThese results show that intracellular levels of Spt6 are fine-tuned by PAAF1 and proteasome, which is required for HIV-1 transcription and extends to cellular genes implicated in cancer.
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