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iASPP regulates neurite development by interacting with Spectrin proteins

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....

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Autores principales: Wang, Junhao, Jia, Chunhong, Gao, Qiong, Zhang, Jiwen, Gu, Xi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10240065/
https://www.ncbi.nlm.nih.gov/pubmed/37284462
http://dx.doi.org/10.3389/fnmol.2023.1154770
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author Wang, Junhao
Jia, Chunhong
Gao, Qiong
Zhang, Jiwen
Gu, Xi
author_facet Wang, Junhao
Jia, Chunhong
Gao, Qiong
Zhang, Jiwen
Gu, Xi
author_sort Wang, Junhao
collection PubMed
description 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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spelling pubmed-102400652023-06-06 iASPP regulates neurite development by interacting with Spectrin proteins Wang, Junhao Jia, Chunhong Gao, Qiong Zhang, Jiwen Gu, Xi Front Mol Neurosci Molecular Neuroscience 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. Frontiers Media S.A. 2023-05-22 /pmc/articles/PMC10240065/ /pubmed/37284462 http://dx.doi.org/10.3389/fnmol.2023.1154770 Text en Copyright © 2023 Wang, Jia, Gao, Zhang and Gu. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Molecular Neuroscience
Wang, Junhao
Jia, Chunhong
Gao, Qiong
Zhang, Jiwen
Gu, Xi
iASPP regulates neurite development by interacting with Spectrin proteins
title iASPP regulates neurite development by interacting with Spectrin proteins
title_full iASPP regulates neurite development by interacting with Spectrin proteins
title_fullStr iASPP regulates neurite development by interacting with Spectrin proteins
title_full_unstemmed iASPP regulates neurite development by interacting with Spectrin proteins
title_short iASPP regulates neurite development by interacting with Spectrin proteins
title_sort iaspp regulates neurite development by interacting with spectrin proteins
topic Molecular Neuroscience
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10240065/
https://www.ncbi.nlm.nih.gov/pubmed/37284462
http://dx.doi.org/10.3389/fnmol.2023.1154770
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