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.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Amino Acid Sequence
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Animals
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Cell Line, Tumor
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Cell Survival*
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Embryonic Stem Cells
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Glioblastoma / drug therapy
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Glioblastoma / metabolism
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Glioblastoma / pathology
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HEK293 Cells
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Humans
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Mice
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Mice, Nude
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Molecular Sequence Data
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Mutation
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PTEN Phosphohydrolase / chemistry*
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PTEN Phosphohydrolase / genetics
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PTEN Phosphohydrolase / metabolism*
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PTEN Phosphohydrolase / pharmacology
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Peptide Chain Initiation, Translational
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Phosphatidylinositol 3-Kinase / metabolism*
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Phosphorylation
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Proto-Oncogene Proteins c-akt / metabolism
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RNA, Messenger / genetics
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RNA, Messenger / metabolism
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Signal Transduction* / drug effects
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Xenograft Model Antitumor Assays
Substances
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RNA, Messenger
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Phosphatidylinositol 3-Kinase
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Proto-Oncogene Proteins c-akt
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PTEN Phosphohydrolase
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PTEN protein, human
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Pten protein, mouse