RETRACTED: Phosphatase and tensin homologue deleted on chromosome 10 (PTEN) has nuclear localization signal-like sequences for nuclear import mediated by major vault protein.
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.
Chung
Ji-Hyun
JH
Clinical Cancer Genetics Program, Human Cancer Genetics Program, Comprehensive Cancer Center, Columbus, Ohio 43210, USA.
Ginn-Pease
Margaret E
ME
Eng
Charis
C
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
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