title: A secreted PTEN phosphatase that enters cells to alter signaling and survival.
abstract: Phosphatase and tensin homolog on chromosome ten (PTEN) is a tumor suppressor and an antagonist of the phosphoinositide-3 kinase (PI3K) pathway. We identified a 576-amino acid translational variant of PTEN, termed PTEN-Long, that arises from an alternative translation start site 519 base pairs upstream of the ATG initiation sequence, adding 173 N-terminal amino acids to the normal PTEN open reading frame. PTEN-Long is a membrane-permeable lipid phosphatase that is secreted from cells and can enter other cells. As an exogenous agent, PTEN-Long antagonized PI3K signaling and induced tumor cell death in vitro and in vivo. By providing a means to restore a functional tumor-suppressor protein to tumor cells, PTEN-Long may have therapeutic uses.
authors.affiliation: Department of Oncological Sciences, Icahn School of Medicine at Mount Sinai, 1470 Madison Avenue, New York, NY 10029, USA.
authors.forename: Benjamin D
authors.initials: BD
authors.lastname: Hopkins
authors.forename: Barry
authors.initials: B
authors.lastname: Fine
authors.forename: Nicole
authors.initials: N
authors.lastname: Steinbach
authors.forename: Meaghan
authors.initials: M
authors.lastname: Dendy
authors.forename: Zachary
authors.initials: Z
authors.lastname: Rapp
authors.forename: Jacquelyn
authors.initials: J
authors.lastname: Shaw
authors.forename: Kyrie
authors.initials: K
authors.lastname: Pappas
authors.forename: Jennifer S
authors.initials: JS
authors.lastname: Yu
authors.forename: Cindy
authors.initials: C
authors.lastname: Hodakoski
authors.forename: Sarah
authors.initials: S
authors.lastname: Mense
authors.forename: Joshua
authors.initials: J
authors.lastname: Klein
authors.forename: Sarah
authors.initials: S
authors.lastname: Pegno
authors.forename: Maria-Luisa
authors.initials: ML
authors.lastname: Sulis
authors.forename: Hannah
authors.initials: H
authors.lastname: Goldstein
authors.forename: Benjamin
authors.initials: B
authors.lastname: Amendolara
authors.forename: Liang
authors.initials: L
authors.lastname: Lei
authors.forename: Matthew
authors.initials: M
authors.lastname: Maurer
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Bruce
authors.forename: Peter
authors.initials: P
authors.lastname: Canoll
authors.forename: Hanina
authors.initials: H
authors.lastname: Hibshoosh
authors.forename: Ramon
authors.initials: R
authors.lastname: Parsons
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D045744:Cell Line, Tumor; D002470:Cell Survival; D053595:Embryonic Stem Cells; D005909:Glioblastoma / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D057809:HEK293 Cells; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D008969:Molecular Sequence Data; D009154:Mutation; D051059:PTEN Phosphohydrolase / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D010442:Peptide Chain Initiation, Translational; D058539:Phosphatidylinositol 3-Kinase / Q000378:metabolism*; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D023041:Xenograft Model Antitumor Assays
chemical_list: D012333:RNA, Messenger; D058539:Phosphatidylinositol 3-Kinase; D051057:Proto-Oncogene Proteins c-akt; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human; C487757:Pten protein, mouse