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Hunter CJ, Remenyi J, Correa SA, et al. MSK1 regulates transcriptional induction of Arc/Arg3.1 in response to neurotrophins. FEBS Open Bio. 2017;7(6):821-834doi: 10.1002/2211-5463.12232.
Hunter, C. J., Remenyi, J., Correa, S. A., Privitera, L., Reyskens, K. M. S. E., Martin, K. J., Toth, R., Frenguelli, B. G., & Arthur, J. S. C. (2017). MSK1 regulates transcriptional induction of Arc/Arg3.1 in response to neurotrophins. FEBS open bio, 7(6), 821-834. https://doi.org/10.1002/2211-5463.12232
Hunter, Chris J, et al. "MSK1 regulates transcriptional induction of Arc/Arg3.1 in response to neurotrophins." FEBS open bio vol. 7,6 (2017): 821-834. doi: https://doi.org/10.1002/2211-5463.12232
Hunter CJ, Remenyi J, Correa SA, Privitera L, Reyskens KMSE, Martin KJ, Toth R, Frenguelli BG, Arthur JSC. MSK1 regulates transcriptional induction of Arc/Arg3.1 in response to neurotrophins. FEBS Open Bio. 2017 May 11;7(6):821-834. doi: 10.1002/2211-5463.12232. eCollection 2017 Jun. PMID: 28593137; PMCID: PMC5458472.
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FEBS Open Bio. 2017 May 11;7(6):821-834. doi: 10.1002/2211-5463.12232. eCollection 2017 Jun.

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

FEBS open bio

Chris J Hunter, Judit Remenyi, Sonia A Correa, Lucia Privitera, Kathleen M S E Reyskens, Kirsty J Martin, Rachel Toth, Bruno G Frenguelli, J Simon C Arthur

Affiliations

  1. MRC Protein Phosphorylation Unit College of Life Sciences Sir James Black Centre University of Dundee UK.
  2. Wellcome Trust Centre for Gene Regulation and Expression Wellcome Trust Building College of Life Sciences University of Dundee UK.
  3. Bradford School of Pharmacy Faculty of Life Sciences University of Bradford UK.
  4. School of Life Sciences University of Warwick Coventry UK.
  5. Division of Cell Signalling and Immunology Wellcome Trust Building College of Life Sciences University of Dundee UK.

PMID: 28593137 PMCID: PMC5458472 DOI: 10.1002/2211-5463.12232

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).

Keywords: Arc/Arg3.1; BDNF; CREB; MSK1; NMDA; glutamate; histone H3; neurotrophins

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