title: RETRACTED: Phosphatase and tensin homologue deleted on chromosome 10 (PTEN) has nuclear localization signal-like sequences for nuclear import mediated by major vault protein.
abstract: Although phosphatase and tensin homologue deleted on chromosome 10 (PTEN) localization in the nucleus and cytoplasm is established, the mechanism is unknown. PTEN is a tumor suppressor phosphatase that causes cell cycle arrest and/or apoptosis. Nuclear-cytoplasmic compartmentalization may be a novel mechanism in regulating these events. PTEN does not contain a traditional nuclear localization sequence (NLS); however, we identified putative NLS-like sequences, which we analyzed by site-directed mutagenesis and localization studies in MCF-7 cells. Two double site mutations exhibited nuclear localization defects. Furthermore, unlike wild-type PTEN, double NLS mutant PTEN did not interact with major vault protein (MVP), a previously hypothesized nuclear-cytoplasmic transport protein. We conclude that these two NLS-like sequences are required for PTEN nuclear import that is mediated by MVP. Further, we show that this MVP-mediated nuclear import is independent of PTEN phosphorylation and of the lipid and protein phosphatase activities of PTEN.
authors.affiliation: Clinical Cancer Genetics Program, Human Cancer Genetics Program, Comprehensive Cancer Center, Columbus, Ohio 43210, USA.
authors.forename: Ji-Hyun
authors.initials: JH
authors.lastname: Chung
authors.forename: Margaret E
authors.initials: ME
authors.lastname: Ginn-Pease
authors.forename: Charis
authors.initials: C
authors.lastname: Eng
mesh_terms: D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000235:genetics / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism; D006801:Humans; D028884:Karyopherins / Q000378:metabolism; D016297:Mutagenesis, Site-Directed; D009154:Mutation; D019913:Nuclear Localization Signals / Q000235:genetics / Q000378:metabolism*; D051059:PTEN Phosphohydrolase; D010744:Phosphoric Monoester Hydrolases / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D013329:Structure-Activity Relationship; D014162:Transfection; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism*; D020394:Vault Ribonucleoprotein Particles / Q000378:metabolism*; D000099187:Major Vault Protein
chemical_list: D028884:Karyopherins; D019913:Nuclear Localization Signals; D051059:PTEN Phosphohydrolase; D010744:Phosphoric Monoester Hydrolases; D025521:Tumor Suppressor Proteins; D020394:Vault Ribonucleoprotein Particles; D000099187:Major Vault Protein; C494929:PTEN protein, human