Nuclear PTEN tumor-suppressor functions through maintaining heterochromatin structure

Lili Gong, Jeane M. Govan, Elizabeth B. Evans, Hui Dai, Edward Wang, Szu Wei Lee, Hui Kuan Lin, Alexander J. Lazar, Gordon B. Mills, Shiaw Yih Lin

    Research output: Contribution to journalArticle

    21 Scopus citations

    Abstract

    The tumor suppressor, PTEN, is one of the most commonly mutated genes in cancer. Recently, PTEN has been shown to localize in the nucleus and is required to maintain genomic stability. Here, we show that nuclear PTEN, independent of its phosphatase activity, is essential for maintaining heterochromatin structure. Depletion of PTEN leads to loss of heterochromatic foci, decreased chromatin compaction, overexpression of heterochromatic genes, and reduced protein stability of heterochromatin protein 1 α. We found that the C-terminus of PTEN is required to maintain heterochromatin structure. Additionally, cancer-associated PTEN mutants lost their tumor-suppressor function when their heterochromatin structure was compromised. We propose that this novel role of PTEN accounts for its function in guarding genomic stability and suppressing tumor development.

    Original languageEnglish (US)
    Pages (from-to)2323-2332
    Number of pages10
    JournalCell Cycle
    Volume14
    Issue number14
    DOIs
    StatePublished - Jan 1 2015

    Keywords

    • Breast cancer
    • HP1α
    • Heterochromatin
    • PTEN
    • Satellite DNA

    ASJC Scopus subject areas

    • Molecular Biology
    • Developmental Biology
    • Cell Biology

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  • Cite this

    Gong, L., Govan, J. M., Evans, E. B., Dai, H., Wang, E., Lee, S. W., Lin, H. K., Lazar, A. J., Mills, G. B., & Lin, S. Y. (2015). Nuclear PTEN tumor-suppressor functions through maintaining heterochromatin structure. Cell Cycle, 14(14), 2323-2332. https://doi.org/10.1080/15384101.2015.1044174