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Publication : iASPP regulates neurite development by interacting with Spectrin proteins.

First Author  Wang J Year  2023
Journal  Front Mol Neurosci Volume  16
Pages  1154770 PubMed ID  37284462
Mgi Jnum  J:336447 Mgi Id  MGI:7488948
Doi  10.3389/fnmol.2023.1154770 Citation  Wang J, et al. (2023) iASPP regulates neurite development by interacting with Spectrin proteins. Front Mol Neurosci 16:1154770
abstractText  INTRODUCTION: Since its discovery in 1999, a substantial body of research has shown that iASPP is highly expressed in various kinds of tumors, interacts with p53, and promotes cancer cell survival by antagonizing the apoptotic activity of p53. However, its role in neurodevelopment is still unknown. METHODS: We studied the role of iASPP in neuronal differentiation through different neuronal differentiation cellular models, combined with immunohistochemistry, RNA interference and gene overexpression, and studied the molecular mechanism involved in the regulation of neuronal development by iASPP through coimmunoprecipitation coupled with mass spectrometry (CoIP-MS) and coimmunoprecipitation (CoIP). RESULTS: In this study, we found that the expression of iASPP gradually decreased during neuronal development. iASPP silencing promotes neuronal differentiation, while its overexpression inhibited neurite differentiation in a variety of neuronal differentiation cellular models. iASPP associated with the cytoskeleton-related protein Sptan1 and dephosphorylated the serine residues in the last spectrin repeat domain of Sptan1 by recruiting PP1. The non-phosphorylated and phosphomimetic mutant form of Sptbn1 inhibited and promoted neuronal cell development respectively. CONCLUSION: Overall, we demonstrate that iASPP suppressed neurite development by inhibiting phosphorylation of Sptbn1.
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