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J. Biol. Chem., Vol. 278, Issue 4, 2758-2766, January 24, 2003
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From the NF-
Post-activation Turn-off of NF-
B-dependent
Transcription Is Regulated by Acetylation of p65*
§,,,
**,,,¶¶
Laboratoire de Virologie Moléculaire,
Institut de Génétique Humaine, Institut de
Génétique Moléculaire, Montpellier 34296, France, the
§§ Departement des Maladies Infectieuses,
Institut Cochin, Paris 75014, France, and the ¶ Department of
Biochemistry, The University of Hong Kong, Hong Kong, China
B represents a family of eukaryotic
transcription factors participating in the regulation of various
cellular genes involved in the immediate early processes of immune,
acute-phase, and inflammatory responses. Cellular localization and
consequently the transcriptional activity of NF-B is tightly
regulated by its partner IB
. Here, we show that the p65 subunit
of NF-B is acetylated by both p300 and PCAF on lysines 122 and 123. Both HDAC2 and HDAC3 interact with p65, although only HDAC3 was able to
deacetylate p65. Acetylation of p65 reduces its ability to bind
B-DNA. Finally, acetylation of p65 facilitated its removal from
DNA and consequently its IB-mediated export from the nucleus.
We propose that acetylation of p65 plays a key role in
IB-mediated attenuation of NF-B transcriptional activity
which is an important process that restores the latent state in
post-induced cells.
*
This work was supported in part by grants from the Agence
Nationale de Recherche sur le SIDA, Human Frontier Science
Program, Minister de la Recherche (ACI) (to M. B.), ARC (to S. E.),
Human Frontier Science Program (to C. S.), and Grants HK-RGC and
HKU (to D.-Y. J.).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.
A Leukemia and Lymphoma Society Scholar.
¶¶
To whom correspondence should be addressed: Laboratoire
de Virologie Moléculaire, Institut de Génétique
Humaine, 141 rue de la Cardonille, Montpellier 34396, France. Tel.:
33-4-99-61-99-32; Fax: 33-4-99-61-99-01; E-mail:
bmonsef@igh.cnrs.fr.
Copyright © 2003 by The American Society for Biochemistry and Molecular Biology, Inc.
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