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