Identification of nucleolus-localized PTEN and its function in regulating ribosome biogenesis

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• 作者：Pingdong Li (1) (2)
  Danni Wang (1) (2)
  Haiyang Li (3)
  Zhenkun Yu (4)
  Xiaohong Chen (1) (2)
  Jugao Fang (1) (2)
  
• 关键词：PTEN ; Nucleolus ; Cell size ; Ribosome biogenesis
• 刊名：Molecular Biology Reports
• 出版年：2014
• 出版时间：October 2014
• 年：2014
• 卷：41
• 期：10
• 页码：6383-6390
• 全文大小：4,757 KB
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• 作者单位：Pingdong Li (1) (2)
  Danni Wang (1) (2)
  Haiyang Li (3)
  Zhenkun Yu (4)
  Xiaohong Chen (1) (2)
  Jugao Fang (1) (2)
  
  1. Department of Otolaryngology, Head and Neck Surgery, Beijing Tongren Hospital, Capital Medical University, Beijing, 100730, People鈥檚 Republic of China
  2. Key Laboratory of Otolaryngology Head and Neck Surgery (Ministry of Education of China), Beijing Institute of Otolaryngology, Beijing, China
  3. Department of Otolaryngology, People鈥檚 Hospital of Beijing Daxing District, Beijing, China
  4. Department of Otolaryngology, Head and Neck Surgery, Medical College, The Affiliated Nanjing Tongren Hospital of the Southeast University, Nanjing, China
  
• ISSN：1573-4978

文摘

The tumor suppressor PTEN is a lipid phosphatase that is found mutated in different types of human cancers. PTEN suppresses cell proliferation by inhibiting the PI3K-Akt signaling pathway at the cell membrane. However, PTEN is also demonstrated to localize in the cell nucleus where it exhibits tumor suppressive activity via a different, unknown mechanism. In this study we report that PTEN also localizes to the nucleolus and that nucleolar PTEN plays an important role in regulating nucleolar homeostasis and maintaining nucleolar morphology. Overexpression of nuclear PTEN in PTEN null cells inhibits Akt phosphorylation and reduces cell size. Knockdown of PTEN in PTEN positive cells leads to nucleolar morphologic changes and an increase in the proportion of cells with a greater number of nucleoli. In addition, knockdown of PTEN in PTEN positive cells increased ribosome biogenesis. These findings expand current understanding of function and relevance of nuclear localized PTEN and provide a foundation for the development of novel therapies targeting PTEN.