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Originally published In Press as doi:10.1074/jbc.M201895200 on April 15, 2002

J. Biol. Chem., Vol. 277, Issue 25, 22215-22221, June 21, 2002
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Tat Acetyl-acceptor Lysines Are Important for Human Immunodeficiency Virus Type-1 Replication*

Vanessa BrèsDagger , Rosemary Kiernan§, Stéphane Emiliani, and Monsef Benkirane||

From the Institut de Génétique Humaine, CNRS UPR 1142, 141 rue de la Cardonille, 34396 Montpellier cedex 5, France

The human immunodeficiency virus type-1 trans-activator Tat is a transcription factor that activates the HIV-1 promoter through binding to the trans-activation-responsive region (TAR) localized at the 5'-end of all viral transcripts. We and others have recently shown that Tat is directly acetylated at lysine 28, within the activation domain, and lysine 50, in the TAR RNA binding domain, by Tat-associated histone acetyltransferases p300, p300/CBP-associating factor, and hGCN5. Here, we show that mutation of acetyl-acceptor lysines to arginine or glutamine affects virus replication. Interestingly, mutation of lysine 28 and lysine 50 differentially affected Tat trans-activation of integrated versus nonintegrated long terminal repeat. Our results highlight the importance of lysine 28 and lysine 50 of Tat in virus replication and Tat-mediated trans-activation.


* This work was supported by grants from the Agence Nationale de Recherche sur le SIDA (ANRS) and Action Concerte Initiative blanche (to M. B.).The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

Dagger Supported by a Ministere de l'Education nationale, de la Recherche et de la Technologie scholarship.

§ Supported by an ANRS fellowship.

Present address: Institut Cochin de Génétique Moléculaire, INSERM U529, 24 rue du Faubourg Saint Jacques, 75014 Paris, France.

|| To whom correspondence should be addressed. Tel.: 33-4-99-61-99-32; Fax: 33-4-99-61-99-01; E-mail: bmonsef@igh.cnrs.fr.


Copyright © 2002 by The American Society for Biochemistry and Molecular Biology, Inc.
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