O-Linked <i>N</i> -Acetylglucosaminylation of Sp1 Inhibits the Human Immunodeficiency Virus Type 1 Promoter is a research paper published in Journal of Virology (2009). On theSindex it has a DataRank of 2.1. It has been cited 41 times, with 40 citing works in its 1-hop citation network.
ABSTRACT Human immunodeficiency virus type 1 (HIV-1) gene expression and replication are regulated by the promoter/enhancer located in the U3 region of the proviral 5′ long terminal repeat (LTR). The binding of cellular transcription factors to specific regulatory sites in the 5′ LTR is a key event in the replication cycle of HIV-1. Since transcriptional activity is regulated by the posttranslational modification of transcription factors with the monosaccharide O-linked N -acetyl- d -glucosamine ( O -GlcNAc), we evaluated whether increased O -GlcNAcylation affects HIV-1 transcription. In the present study we demonstrate that treatment of HIV-1-infected lymphocytes with the O -GlcNAcylation-enhancing agent glucosamine (GlcN) repressed viral transcription in a dose-dependent manner. Overexpression of O -GlcNAc transferase (OGT), the sole known enzyme catalyzing the addition of O -GlcNAc to proteins, specifically inhibited the activity of the HIV-1 LTR promoter in different T-cell lines and in primary CD4 + T lymphocytes. Inhibition of HIV-1 LTR activity in infected T cells was most efficient (>95%) when OGT was recombinantly overexpressed prior to infection. O -GlcNAcylation of the transcription factor Sp1 and the presence of Sp1-binding sites in the LTR were found to be crucial for this inhibitory effect. From this study, we conclude that O -GlcNAcylation of Sp1 inhibits the activity of the HIV-1 LTR promoter. Modulation of Sp1 O -GlcNAcylation may play a role in the regulation of HIV-1 latency and activation and links viral replication to the glucose metabolism of the host cell. Hence, the establishment of a metabolic treatment might supplement the repertoire of antiretroviral therapies against AIDS.
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Base Score Contribution
0.561
From this paper's citation signal
Citation Network Contribution
1.6
From 37 citing papers with measurable signal
Ranked by citation count — the same ordering the engine uses when summing log1p(Cq) over citers.
DataRank blends this paper's own citation count with the influence of the papers that cite it. Here, roughly 26% comes from its base citations and 74% from the citation network (37 citing papers contributed measurable signal).
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