Nuclear PTEN tumor-suppressor functions through maintaining heterochromatin structure

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 heterochroma...

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Bibliographic Details
Published in:	Cell Cycle 2015, Vol.14 (14), p.2323-2332
Main Authors:	Gong, Lili, Govan, Jeane M, Evans, Elizabeth B, Dai, Hui, Wang, Edward, Lee, Szu-Wei, Lin, Hui-Kuan, Lazar, Alexander J, Mills, Gordon B, Lin, Shiaw-Yih
Format:	Report
Language:	eng
Subjects:	breast cancer heterochromatin HP1α PTEN satellite DNA
Online Access:	Get full text
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Summary:	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.
ISSN:	1538-4101 1551-4005