title: Nuclear PTEN tumor-suppressor functions through maintaining heterochromatin structure.
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.
authors.affiliation: a Department of Systems Biology ; The University of Texas MD Anderson Cancer Center ; Houston , TX USA.
authors.forename: Lili
authors.initials: L
authors.lastname: Gong
authors.forename: Jeane M
authors.initials: JM
authors.lastname: Govan
authors.forename: Elizabeth B
authors.initials: EB
authors.lastname: Evans
authors.forename: Hui
authors.initials: H
authors.lastname: Dai
authors.forename: Edward
authors.initials: E
authors.lastname: Wang
authors.forename: Szu-Wei
authors.initials: SW
authors.lastname: Lee
authors.forename: Hui-Kuan
authors.initials: HK
authors.lastname: Lin
authors.forename: Alexander J
authors.initials: AJ
authors.lastname: Lazar
authors.forename: Gordon B
authors.initials: GB
authors.lastname: Mills
authors.forename: Shiaw-Yih
authors.initials: SY
authors.lastname: Lin
mesh_terms: D000818:Animals; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D000090266:Chromobox Protein Homolog 5; D002867:Chromones / Q000494:pharmacology; D002868:Chromosomal Proteins, Non-Histone / Q000378:metabolism; D006570:Heterochromatin / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D047468:Immunoprecipitation; D051379:Mice; D009025:Morpholines / Q000494:pharmacology; D051059:PTEN Phosphohydrolase / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D000081082:Phosphoinositide-3 Kinase Inhibitors; D017434:Protein Structure, Tertiary; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism
chemical_list: D000090266:Chromobox Protein Homolog 5; D002867:Chromones; D002868:Chromosomal Proteins, Non-Histone; D006570:Heterochromatin; D009025:Morpholines; D051059:PTEN Phosphohydrolase; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D034741:RNA, Small Interfering; C000715594:CBX5 protein, human; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; C494929:PTEN protein, human
keywords: HP1α; PTEN; breast cancer; heterochromatin; satellite DNA