iASPP regulates neurite development by interacting with Spectrin proteins
IntroductionSince 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.Met...
| Main Authors: | , , , , |
|---|---|
| 格式: | 文件 |
| 语言: | English |
| 出版: |
Frontiers Media S.A.
2023-05-01
|
| 丛编: | Frontiers in Molecular Neuroscience |
| 主题: | |
| 在线阅读: | https://www.frontiersin.org/articles/10.3389/fnmol.2023.1154770/full |
| _version_ | 1827943024862167040 |
|---|---|
| author | Junhao Wang Chunhong Jia Qiong Gao Jiwen Zhang Xi Gu |
| author_facet | Junhao Wang Chunhong Jia Qiong Gao Jiwen Zhang Xi Gu |
| author_sort | Junhao Wang |
| collection | DOAJ |
| description | IntroductionSince 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.MethodsWe 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).ResultsIn 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.ConclusionOverall, we demonstrate that iASPP suppressed neurite development by inhibiting phosphorylation of Sptbn1. |
| first_indexed | 2024-03-13T10:09:15Z |
| format | Article |
| id | doaj.art-21735db7992a4f109e0d2a5c55f4e10c |
| institution | Directory Open Access Journal |
| issn | 1662-5099 |
| language | English |
| last_indexed | 2024-03-13T10:09:15Z |
| publishDate | 2023-05-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Molecular Neuroscience |
| spelling | doaj.art-21735db7992a4f109e0d2a5c55f4e10c2023-05-22T04:56:07ZengFrontiers Media S.A.Frontiers in Molecular Neuroscience1662-50992023-05-011610.3389/fnmol.2023.11547701154770iASPP regulates neurite development by interacting with Spectrin proteinsJunhao Wang0Chunhong Jia1Qiong Gao2Jiwen Zhang3Xi Gu4Fujian Key Laboratory for Translational Research in Cancer and Neurodegenerative Diseases, Institute for Translational Medicine, School of Basic Medical Sciences, Fujian Medical University, Fuzhou, ChinaDepartment of Neonatology, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, ChinaFujian Key Laboratory for Translational Research in Cancer and Neurodegenerative Diseases, Institute for Translational Medicine, School of Basic Medical Sciences, Fujian Medical University, Fuzhou, ChinaFujian Key Laboratory for Translational Research in Cancer and Neurodegenerative Diseases, Institute for Translational Medicine, School of Basic Medical Sciences, Fujian Medical University, Fuzhou, ChinaFujian Key Laboratory for Translational Research in Cancer and Neurodegenerative Diseases, Institute for Translational Medicine, School of Basic Medical Sciences, Fujian Medical University, Fuzhou, ChinaIntroductionSince 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.MethodsWe 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).ResultsIn 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.ConclusionOverall, we demonstrate that iASPP suppressed neurite development by inhibiting phosphorylation of Sptbn1.https://www.frontiersin.org/articles/10.3389/fnmol.2023.1154770/fulliASPPSptan1Sptbn1phosphorylation modificationneurite development |
| spellingShingle | Junhao Wang Chunhong Jia Qiong Gao Jiwen Zhang Xi Gu iASPP regulates neurite development by interacting with Spectrin proteins Frontiers in Molecular Neuroscience iASPP Sptan1 Sptbn1 phosphorylation modification neurite development |
| 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 | iASPP Sptan1 Sptbn1 phosphorylation modification neurite development |
| url | https://www.frontiersin.org/articles/10.3389/fnmol.2023.1154770/full |
| work_keys_str_mv | AT junhaowang iasppregulatesneuritedevelopmentbyinteractingwithspectrinproteins AT chunhongjia iasppregulatesneuritedevelopmentbyinteractingwithspectrinproteins AT qionggao iasppregulatesneuritedevelopmentbyinteractingwithspectrinproteins AT jiwenzhang iasppregulatesneuritedevelopmentbyinteractingwithspectrinproteins AT xigu iasppregulatesneuritedevelopmentbyinteractingwithspectrinproteins |