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題 名 | PPP2R2B Bβ1/Bβ2 Isoform and Role in Regulation of Cell Proliferation=PPP2R2B Bβ1及Bβ2 Isoform及其在細胞增生調節的角色 |
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作 者 | 林志信; 李桂楨; | 書刊名 | BioFormosa |
卷 期 | 44:2 2009.12[民98.12] |
頁 次 | 頁75-82 |
分類號 | 364 |
關鍵詞 | 細胞增生調節; PPP2R2B; Bβ1 and Bβ2 isoforms; Cell proliferation regulation; |
語 文 | 英文(English) |
中文摘要 | 摘 要 PPP2R2B (Bβ)為廣泛表現在腦部的去磷酸酶PP2A 的調控次單位。啟動子的差異使用及選擇性 裁接,產生N 端相異的Bβ1 及Bβ2 兩種isoform,分別使PP2A 主要作用在細胞內不同部位。Bβ 在神經細胞存活上扮演重要角色。Bβ1/Bβ2 表現的改變會影響PP2A 活性,進而導致神經退化性疾 病。為檢視Bβ 調控的PP2A 在神經退化性疾病的角色,我們建立了誘導性Bβ1/Bβ2 細胞株。Myc 標記的Bβ1、Bβ2 蛋白的誘導表現後,分別被標的至細胞質或粒線體。Bβ 細胞株的細胞週期分析 顯示,在Bβ2 表現的細胞中,subG1 及G2/M 期顯著增加,並伴隨著顯著的細胞增生遲緩及抑制性 磷酸化Cdc2 蛋白增加。我們的實驗結果顯示,抑制Bβ2 表現可能被發展為有潛能的治療策略,來 治療與PP2A/ Bβ2 活性增加相關的神經退化性疾病。 |
英文摘要 | ABSTRACT PPP2R2B (Bβ) is an important regulator of protein phosphatase 2A (PP2A) activity in the brain. Through differential promoter usage and alternative splicing, two major isoforms Bβ1 and Bβ2 with divergent sub-cellular targeting N termini are produced. Bβ plays an important role in neuronal survival. Altered Bβ1/Bβ2 expression would be reflected by abnormal PP2A activity to predispose to neurodegenerative diseases. In this study we established inducible Bβ1/Bβ2 cell lines to investigate the role of Bβ-modulating PP2A in neuronal degeneration. The induced Myc-tagged Bβ1/Bβ2 proteins were mainly localized in cytoplasm and mitochondria, respectively. Cell cycle analysis of Bβ cell lines revealed a significant increase in the cell population at subG1 and G2/M phases in Bβ2-expressing cells, accompanying with significant reduced cell proliferation and increased inhibitory phosphorylation of cell division cycle 2. Taken together, these results suggest that inhibition of Bβ2 expression may be an attractive avenue for developing potential therapeutic strategies to treat neurodegenerative disorders related to increased PP2A/Bβ2 activity. |
本系統中英文摘要資訊取自各篇刊載內容。