MeCP2 S421 phosphorylation mediates neurogenesis via Notch signaling pathway

 

 

The phosphorylation of Methyl-CpG-binding protein 2 (MeCP2) at serine 421 (S421) have been shown is necessary for regulation of neurogenesis. It is induced by neuronal activity in postmitotic neurons. Li et al. identified the Notch signaling is involved in the regulation of MeCP2 S421 phosphorylation other than neuronal activity. The article was published on Nature Communication, recently.

 

In this study, researchers isolated adult neuroprogenitor cells (aNPCs) from mouse hippocampus, and found MeCP2 S421 was phosphorylated in response to aurora kinase B, which is a functional protein related to mitosis ,indicating the phosphorylation is linked to cell cycle. They also found the phospho-mutation of MeCP2 S421 altered the proliferation and differentiation balance of aNPCs. Moreover, the regulation of cell proliferation/differentiation is mediated by MeCP2 S421 phosphorylation via a downstream factor of S421, Notch signaling. The transcription level of both ligand and receptor of Notch signaling are regulated directly by MeCP2 phosphorylation. In contrast to previous studies that focused on the expression level of MeCP2, this study emphasizes the phosphorylation, and reveals a novel role of MeCP2 as a regulatory switch in postmitotic neurons.

 

Reference:
Nat Commun. 2014 Nov 25;5:5601.

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S1529	Hesperadin	Hesperadin potently inhibits Aurora B with IC50 of 250 nM in a cell-free assay. It markedly reduces the activity of AMPK, Lck, MKK1, MAPKAP-K1, CHK1 and PHK while it does not inhibit MKK1 activity in vivo.
S7399	FLI-06	FLI-06 is a novel inhibitor of Notch signaling with EC50 of 2.3 μM.

Related Targets

Aurora Kinase Gamma-secretase