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MSK1 regulates transcriptional induction of Arc/Arg3.1 in response to neurotrophins.

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Hunter, Chris J., Remenyi, Judit, Correa, Sonia A., Privitera, Lucia, Reyskens, Kathleen M. S. E., Martin, Kirsty J., Toth, Rachel, Frenguelli, Bruno G. and Arthur, J. Simon C. (2017) MSK1 regulates transcriptional induction of Arc/Arg3.1 in response to neurotrophins. FEBS Open Bio, 7 (6). pp. 821-834. doi:10.1002/2211-5463.12232

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Official URL: http://dx.doi.org/10.1002/2211-5463.12232

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Abstract

The immediate early gene activity-regulated cytoskeletal protein (Arc)/Arg3.1 and the neurotrophin brain-derived neurotrophic factor (BDNF) play important roles in synaptic plasticity and learning and memory in the mammalian brain. However, the mechanisms by which BDNF regulates the expression of Arc/Arg3.1 are unclear. In this study, we show that BDNF acts via the ERK1/2 pathway to activate the nuclear kinase mitogen- and stress-activated protein kinase 1 (MSK1). MSK1 then induces Arc/Arg3.1 expression via the phosphorylation of histone H3 at the Arc/Arg3.1 promoter. MSK1 can also phosphorylate the transcription factor cyclic-AMP response element-binding protein (CREB) on Ser133. However, this is not required for BDNF-induced Arc.Arg3.1 transcription as a Ser133Ala knockin mutation had no effect on Arc/Arg3.1 induction. In parallel, ERK1/2 directly activates Arc/Arg3.1 mRNA transcription via at least one serum response element on the promoter, which bind a complex of the Serum Response Factor (SRF) and a Ternary Complex Factor (TCF).

Item Type: Journal Article
Subjects: Q Science > QP Physiology
Divisions: Faculty of Science > Life Sciences (2010- )
Library of Congress Subject Headings (LCSH): Neuroplasticity, Neurotrophic functions, Protein kinases, Genetic transcription -- Regulation
Journal or Publication Title: FEBS Open Bio
Publisher: John Wiley & Sons Ltd.
ISSN: 2211-5463
Official Date: 11 May 2017
Dates:
DateEvent
11 May 2017Published
31 March 2017Accepted
13 December 2016Submitted
Volume: 7
Number: 6
Page Range: pp. 821-834
DOI: 10.1002/2211-5463.12232
Status: Peer Reviewed
Publication Status: Published
Access rights to Published version: Open Access
Funder: Wellcome Trust (London, England), Biotechnology and Biological Sciences Research Council (Great Britain) (BBSRC), Medical Research Council (Great Britain) (MRC), WPH Charitable Trust
RIOXX Funder/Project Grant:
Project/Grant IDRIOXX Funder NameFunder ID
UNSPECIFIEDWellcome Trusthttp://dx.doi.org/10.13039/100010269
UNSPECIFIED[BBSRC] Biotechnology and Biological Sciences Research Councilhttp://dx.doi.org/10.13039/501100000268
UNSPECIFIED[MRC] Medical Research Councilhttp://dx.doi.org/10.13039/501100000265
UNSPECIFIEDWPH Charitable Trusthttp://dx.doi.org/10.13039/100012362

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