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 Mills, Shiaw Yih Lin

Research output: Contribution to journalArticle

16 Citations (Scopus)

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
Externally publishedYes

Fingerprint

Heterochromatin
Genomic Instability
Neoplasms
Protein Stability
Neoplasm Genes
Phosphoric Monoester Hydrolases
Chromatin
Proteins

Keywords

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

ASJC Scopus subject areas

  • Molecular Biology
  • Developmental Biology
  • Cell Biology

Cite this

Gong, L., Govan, J. M., Evans, E. B., Dai, H., Wang, E., Lee, S. W., ... 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

Nuclear PTEN tumor-suppressor functions through maintaining heterochromatin structure. / Gong, Lili; Govan, Jeane M.; Evans, Elizabeth B.; Dai, Hui; Wang, Edward; Lee, Szu Wei; Lin, Hui Kuan; Lazar, Alexander J.; Mills, Gordon; Lin, Shiaw Yih.

In: Cell Cycle, Vol. 14, No. 14, 01.01.2015, p. 2323-2332.

Research output: Contribution to journalArticle

Gong, L, Govan, JM, Evans, EB, Dai, H, Wang, E, Lee, SW, Lin, HK, Lazar, AJ, Mills, G & Lin, SY 2015, 'Nuclear PTEN tumor-suppressor functions through maintaining heterochromatin structure', Cell Cycle, vol. 14, no. 14, pp. 2323-2332. https://doi.org/10.1080/15384101.2015.1044174
Gong, Lili ; Govan, Jeane M. ; Evans, Elizabeth B. ; Dai, Hui ; Wang, Edward ; Lee, Szu Wei ; Lin, Hui Kuan ; Lazar, Alexander J. ; Mills, Gordon ; Lin, Shiaw Yih. / Nuclear PTEN tumor-suppressor functions through maintaining heterochromatin structure. In: Cell Cycle. 2015 ; Vol. 14, No. 14. pp. 2323-2332.
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