PCP4/PEP19は、ヒト神経芽腫M17において、 Ascl1 および NeuroD1 発現の転写制御を介して神経突起の伸長を制御する。

Material type: 博士論文

Author: 北薗, 育美

Publisher: nature

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Material Format: Digital

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Name of awarding university/degree: 鹿児島大学,博士(医学),Doctor of Philosophy in Medical Science

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Note (General)：: 博士論文全文, 博士論文要旨, 最終試験結果の要旨, 論文審査の要旨Purkinje cell protein 4/peptide 19 (PCP4/PEP19) is 7.6 kDa peptide originally found in Purkinje cells. PCP4/PEP19 is...

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Material Type: 博士論文
Title: PCP4/PEP19は、ヒト神経芽腫M17において、 Ascl1 および NeuroD1 発現の転写制御を介して神経突起の伸長を制御する。
Author/Editor: 北薗, 育美
Author Heading: 北薗, 育美キタゾノ, イクミ
Publication, Distribution, etc.: nature
Alternative Title: PCP4/PEP19 downregulates neurite outgrowth via transcriptional regulation of Ascl1 and NeuroD1 expression in human neuroblastoma M17 cells
Degree grantor/type: 鹿児島大学
Date Granted: 2021-08-11
Dissertation Number: 乙総論第41号
Degree Type: 博士(医学)
Doctor of Philosophy in Medical Science
Text Language Code: eng
Target Audience: 一般
Note (General): 博士論文全文, 博士論文要旨, 最終試験結果の要旨, 論文審査の要旨
Purkinje cell protein 4/peptide 19 (PCP4/PEP19) is 7.6 kDa peptide originally found in Purkinje cells. PCP4/PEP19 is a differentiation maker of Purkinje cells, where it functions as an antiapoptotic factor. Cerebral neuronal cells also express PCP4/PEP19, which may be related to neuronal cell survival. However, evidence suggests that PCP4/PEP19 may also be involved in neuronal differentiation. Here, we investigated the effects of PCP4/PEP19 expression on neuronal differentiation by analyzing neurite outgrowth, and expression of neuronal differentiation markers in cultured human neuroblastoma M17 cells. When PCP4/PEP19 expression was reduced by siRNA-mediated knockdown, neurite outgrowth was significantly increased. Among many differentiation markers tested, expression of NeuroD1 was increased, while that of Ascl1 was decreased upon PCP4/PEP19 knockdown. Furthermore, luciferase reporter assays revealed that PCP4/PEP19 knockdown upregulated NeuroD1 and downregulated Ascl1 expression, at the transcriptional level. These results suggest a new function of PCP4/PEP19, which suppresses neurite outgrowth and neuronal differentiation through the regulation of NeuroD1 and Ascl1 expression in M17 cells. Furthermore, immunohistochemical studies showed that PCP4/PEP19 localizes in the nuclei of human neuroblastoma cells. Therefore, PCP4/PEP19 may also be an intranuclear negative regulator of neuronal differentiation and may thus be a potential therapeutic target to promote cellular differentiation in human neuroblastoma. Ikumi Kitazono, Taiji Hamada, Takuya Yoshimura, Mari Kirishima, Seiya Yokoyama, Toshiaki Akahane & Akihide Tanimoto PCP4/PEP19 downregulates neurite outgrowth via transcriptional regulation of Ascl1 and NeuroD1 expression in human neuroblastoma M17 cells Laboratory Investigation 100, p.1551–1563 (2020) https://doi.org/10.1038/s41374-020-0462-z
Format (IMT): application/pdf
Source: Diss_北薗_育美_ISK41_2021 （fulltext）
https://ir.kagoshima-u.ac.jp/record/15896/files/Diss_%E5%8C%97%E8%96%97_%E8%82%B2%E7%BE%8E_ISK41_2021.pdf
Access Restrictions: インターネット公開
Data Provider (Database): 国立情報学研究所 : 学術機関リポジトリデータベース（IRDB）（機関リポジトリ）
https://irdb.nii.ac.jp
Original Data Provider (Database): 鹿児島大学 : 鹿児島大学リポジトリ