| First Author | Hunter CJ | Year | 2017 |
| Journal | FEBS Open Bio | Volume | 7 |
| Issue | 6 | Pages | 821-834 |
| PubMed ID | 28593137 | Mgi Jnum | J:310966 |
| Mgi Id | MGI:6764970 | Doi | 10.1002/2211-5463.12232 |
| Citation | Hunter CJ, et al. (2017) MSK1 regulates transcriptional induction of Arc/Arg3.1 in response to neurotrophins. FEBS Open Bio 7(6):821-834 |
| abstractText | 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). |
