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SIRT1 regulates HIV transcription via Tat deacetylation

Pagans, S and Pedal, A and North, BJ and Kaehlcke, K and Marshall, BL and Dorr, A and Hetzer-Egger, C and Henklein, P and Frye, R and McBurney, MW and Hruby, H and Jung, M and Verdin, E and Ott, M (2005) SIRT1 regulates HIV transcription via Tat deacetylation. PLoS Biology, 3 (2). 0210 - 0220. ISSN 1544-9173

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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. Copyright: © 2005 Pagans et al.


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Item Type: Article
Status: Published
CreatorsEmailPitt UsernameORCID
Pagans, S
Pedal, A
North, BJ
Kaehlcke, K
Marshall, BL
Dorr, A
Hetzer-Egger, C
Henklein, P
Frye, Rfrye01@pitt.eduFRYE01
McBurney, MW
Hruby, H
Jung, M
Verdin, E
Ott, M
Date: 1 January 2005
Date Type: Publication
Journal or Publication Title: PLoS Biology
Volume: 3
Number: 2
Page Range: 0210 - 0220
DOI or Unique Handle: 10.1371/journal.pbio.0030041
Refereed: Yes
ISSN: 1544-9173
PubMed Central ID: PMC546329
PubMed ID: 15719057
Date Deposited: 11 Jul 2012 18:05
Last Modified: 07 Feb 2019 02:55


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