Previous Article | Next Article ![]()
Molecular and Cellular Biology, October 2001, p. 7089-7096, Vol. 21, No. 20
Institut de Génétique et de
Biologie Moléculaire et Cellulaire, CNRS, INSERM,
Université Louis Pasteur, 67404 Illkirch,
Strasbourg,1 and CNRS UPR 9079,
94800 Villejuif,2 France
Received 16 April 2001/Returned for modification 7 June
2001/Accepted 11 July 2001
The protein kinase ribosomal S6 kinase 2 (RSK2) has been implicated
in phosphorylation of transcription factor CREB and histone H3 in
response to mitogenic stimulation by epidermal growth factor. Binding
of phospho-CREB to the coactivator CBP allows gene activation through
recruitment of the basal transcriptional machinery. Acetylation of H3
by histone acetyltransferase (HAT) activities, such as the one carried
by CBP, has been functionally coupled to H3 phosphorylation. While
various lines of evidence indicate that coupled histone acetylation and
phosphorylation may act in concert to induce chromatin remodeling
events facilitating gene activation, little is known about the coupling
of the two processes at the signaling level. Here we show that CBP and
RSK2 are associated in a complex in quiescent cells and that they
dissociate within a few minutes upon mitogenic stimulus. CBP
preferentially interacts with unphosphorylated RSK2 in a complex where
both RSK2 kinase activity and CBP acetylase activity are inhibited.
Dissociation is dependent on phosphorylation of RSK2 on Ser227 and
results in stimulation of both kinase and HAT activities. We propose a
model in which dynamic formation and dissociation of the CBP-RSK2
complex in response to mitogenic stimulation allow regulated
phosphorylation and acetylation of specific substrates, leading to
coordinated modulation of gene expression.
0270-7306/01/$04.00+0 DOI: 10.1128/MCB.21.20.7089-7096.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.
Mitogen-Regulated RSK2-CBP Interaction Controls
Their Kinase and Acetylase Activities
*
Corresponding author. Mailing address: Institut de
Génétique et de Biologie Moléculaire et Cellulaire,
CNRS, INSERM, Université Louis Pasteur, 1, rue Laurent Fries,
67404 Illkirch, Strasbourg, France. Phone: 33 388 653410. Fax: 33 388 653246. E-mail: paolosc{at}igbmc.u-strasbg.fr.
This article has been cited by other articles:
| J. Bacteriol. | J. Virol. | Eukaryot. Cell |
|---|
| Microbiol. Mol. Biol. Rev. | Clin. Vaccine Immunol. | All ASM Journals |
|---|