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Cited by 331

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SIRT1 Regulates HIV Transcription via Tat Deacetylation

Open access
Pagans, Sara, Pedal, Angelika, North, Brian J, Kaehlcke, Katrin, Marshall, Brett L, Dorr, Alexander, Hetzer-Egger, Claudia, Henklein, Peter, Frye, Roy, McBurney, Michael W, Hruby, Henning, Jung, Manfred, Verdin, Eric, Ott, Melanie·2005·PLoS Biology
DOI 10.1371/journal.pbio.0030041
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Abstract

The human immunodeficiency virus (HIV) Tat protein is acetylated by the transcriptional coactivator p300, a necessary step in Tat-mediated transactivation. We report here that Tat is deacetylated by human sirtuin 1 (SIRT1), a nicotinamide adenine dinucleotide-dependent class III protein deacetylase in vitro and in vivo. Tat and SIRT1 coimmunoprecipitate and synergistically activate the HIV promoter. Conversely, knockdown of SIRT1 via small interfering RNAs or treatment with a novel small molecule inhibitor of the SIRT1 deacetylase activity inhibit Tat-mediated transactivation of the HIV long terminal repeat. Tat transactivation is defective in SIRT1-null mouse embryonic fibroblasts and can be rescued by expression of SIRT1. These results support a model in which cycles of Tat acetylation and deacetylation regulate HIV transcription. SIRT1 recycles Tat to its unacetylated form and acts as a transcriptional coactivator during Tat transactivation.

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Cited by

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Metadata

Authors
Pagans, S., Pedal, A., North, B. J., Kaehlcke, K., Marshall, B. L., Dorr, A., Hetzer-Egger, C., Henklein, P., Frye, R., McBurney, M. W., Hruby, H., Jung, M., Verdin, E., & Ott, M.
Venue
PLoS Biology
Publisher
Public Library of Science (PLoS)
Published
2005-02-08
Volume
3
Issue
2
Pages
e41
ISSN
  • 1544-9173 (ISSN-L)
  • 1545-7885
DOI
10.1371/journal.pbio.0030041
OpenAlex
W2078673393
Cited by
331
References
8
FWCI
7.15
Type
journal article
Language
en
Open access
gold
Licence
creativecommons.org/licenses/by/4.0/ (unspecified)

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CoChat. (2026). Citation check: SIRT1 Regulates HIV Transcription via Tat Deacetylation. https://app.cochat.ai/papers/10.1371/journal.pbio.0030041
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Pagans, S., Pedal, A., North, B. J., Kaehlcke, K., Marshall, B. L., Dorr, A., Hetzer-Egger, C., Henklein, P., Frye, R., McBurney, M. W., Hruby, H., Jung, M., Verdin, E., & Ott, M. (2005). SIRT1 Regulates HIV Transcription via Tat Deacetylation. PLoS Biology. https://doi.org/10.1371/journal.pbio.0030041

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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).

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