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Publication : PTEN-GSK3β-MOB1 axis controls neurite outgrowth in vitro and in vivo.

First Author  Song Z Year  2018
Journal  Cell Mol Life Sci Volume  75
Issue  23 Pages  4445-4464
PubMed ID  30069702 Mgi Jnum  J:316118
Mgi Id  MGI:6831793 Doi  10.1007/s00018-018-2890-0
Citation  Song Z, et al. (2018) PTEN-GSK3beta-MOB1 axis controls neurite outgrowth in vitro and in vivo. Cell Mol Life Sci 75(23):4445-4464
abstractText  Mps One binder 1 (MOB1) is a core component of NDR/LATS kinase and a positive regulator of the Hippo signaling pathway. However, its role in neurite outgrowth still remains to be clarified. Here, we confirmed, for the first time, that MOB1 promoted neurite outgrowth and was involved in functional recovery after spinal cord injury (SCI) in mice. Mechanistically, we found that MOB1 stability was regulated by the PTEN-GSK3beta axis. The MOB1 protein was significantly up-regulated in PTEN-knockdown neuronal cells. This effect was dependent on the lipid phosphatase activity of PTEN. Moreover, MOB1 was found to be a novel substrate for GSK3beta that is phosphorylated on serine 146 and degraded via the ubiquitin-proteasome system (UPS). Finally, in vivo lentiviral-mediated silencing of PTEN promoted neurite outgrowth and functional recovery after SCI and this effect was reversed by down-regulation of MOB1. Taken together, this study provided mechanistic insight into how MOB1 acts as a novel and a necessary regulator in PTEN-GSK3beta axis that controls neurite outgrowth after SCI.
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