title: PNUTS functions as a proto-oncogene by sequestering PTEN.
abstract: PTEN is a well-defined tumor suppressor gene that antagonizes the PI3K/Akt pathway to regulate a multitude of cellular processes, such as survival, growth, motility, invasiveness, and angiogenesis. While the functions of PTEN have been studied extensively, the regulation of its activity during normal and disease conditions still remains incompletely understood. In this study, we identified the protein phosphatase-1 nuclear targeting subunit PNUTS (PPP1R10) as a PTEN-associated protein. PNUTS directly interacted with the lipid-binding domain (C2 domain) of PTEN and sequestered it in the nucleus. Depletion of PNUTS leads to increased apoptosis and reduced cellular proliferation in a PTEN-dependent manner. PNUTS expression was elevated in certain cancers compared with matched normal tissues. Collectively, our studies reveal PNUTS as a novel PTEN regulator and a likely oncogene.
authors.affiliation: Laboratory of Cell Death & Cell Survival, Centre for DNA Fingerprinting and Diagnostics (CDFD), Nampally, India.
authors.forename: Sridhar
authors.initials: S
authors.lastname: Kavela
authors.forename: Swapnil R
authors.initials: SR
authors.lastname: Shinde
authors.forename: Raman
authors.initials: R
authors.lastname: Ratheesh
authors.forename: Kotapalli
authors.initials: K
authors.lastname: Viswakalyan
authors.forename: Murali D
authors.initials: MD
authors.lastname: Bashyam
authors.forename: Swarnalata
authors.initials: S
authors.lastname: Gowrishankar
authors.forename: Mohana
authors.initials: M
authors.lastname: Vamsy
authors.forename: Sujit
authors.initials: S
authors.lastname: Pattnaik
authors.forename: Subramanyeshwar
authors.initials: S
authors.lastname: Rao
authors.forename: Regulagadda A
authors.initials: RA
authors.lastname: Sastry
authors.forename: Mukta
authors.initials: M
authors.lastname: Srinivasulu
authors.forename: Junjie
authors.initials: J
authors.lastname: Chen
authors.forename: Subbareddy
authors.initials: S
authors.lastname: Maddika
mesh_terms: D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D005455:Fluorescent Antibody Technique; D006801:Humans; D015151:Immunoblotting; D007150:Immunohistochemistry; D047468:Immunoprecipitation; D009369:Neoplasms / Q000235:genetics / Q000378:metabolism*; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D051059:PTEN Phosphohydrolase / Q000378:metabolism*; D021381:Protein Transport / Q000502:physiology; D000090063:Proto-Oncogene Mas; D011519:Proto-Oncogenes / Q000502:physiology*; D034622:RNA Interference; D034741:RNA, Small Interfering; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014162:Transfection
chemical_list: D004268:DNA-Binding Proteins; C000715470:MAS1 protein, human; D009687:Nuclear Proteins; C110225:PPP1R10 protein, human; D000090063:Proto-Oncogene Mas; D034741:RNA, Small Interfering; D016601:RNA-Binding Proteins; D051059:PTEN Phosphohydrolase