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

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Abstract

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.

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Acknowledgments

This research was supported by the following grants: Research Fund for the Doctoral Program of Higher Education (20101107110005), Beijing Natural Science Foundation (7122039).

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Authors and Affiliations

  1. Department of Otolaryngology, Head and Neck Surgery, Beijing Tongren Hospital, Capital Medical University, Beijing, 100730, People’s Republic of China

    Pingdong Li, Danni Wang, Xiaohong Chen & Jugao Fang

  2. Key Laboratory of Otolaryngology Head and Neck Surgery (Ministry of Education of China), Beijing Institute of Otolaryngology, Beijing, China

    Pingdong Li, Danni Wang, Xiaohong Chen & Jugao Fang

  3. Department of Otolaryngology, People’s Hospital of Beijing Daxing District, Beijing, China

    Haiyang Li

  4. Department of Otolaryngology, Head and Neck Surgery, Medical College, The Affiliated Nanjing Tongren Hospital of the Southeast University, Nanjing, China

    Zhenkun Yu

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  1. Pingdong Li
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  4. Zhenkun Yu
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Correspondence to Pingdong Li.

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Pingdong Li and Danni Wang authors are contributed equally to this work.

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Li, P., Wang, D., Li, H. et al. Identification of nucleolus-localized PTEN and its function in regulating ribosome biogenesis. Mol Biol Rep 41, 6383–6390 (2014). https://doi.org/10.1007/s11033-014-3518-6

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  • DOI: https://doi.org/10.1007/s11033-014-3518-6

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