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Plos Biology : Sirt1 Regulates Hiv Transcription Via Tat Deacetylation, Volume 3

By Emerman, Michael

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Book Id: WPLBN0003924149
Format Type: PDF eBook :
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Reproduction Date: 2015

Title: Plos Biology : Sirt1 Regulates Hiv Transcription Via Tat Deacetylation, Volume 3  
Author: Emerman, Michael
Volume: Volume 3
Language: English
Subject: Journals, Science, Biology
Collections: Periodicals: Journal and Magazine Collection (Contemporary), PLoS Biology
Publication Date:
Publisher: Plos


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Emerman, M. (n.d.). Plos Biology : Sirt1 Regulates Hiv Transcription Via Tat Deacetylation, Volume 3. Retrieved from

Description : 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 Tatmediated 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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