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PMID: 23744781 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

A secreted PTEN phosphatase that enters cells to alter signaling and survival.

Science (New York, N.Y.) ·Vol. 341 ·No. 6144 ·2013-07-26 ·Pages 399-402

Hopkins BD, Fine B, Steinbach N, Dendy M, Rapp Z, Shaw J, Pappas K, Yu JS, Hodakoski C, Mense S, Klein J, Pegno S, Sulis ML, Goldstein H, Amendolara B, Lei L, Maurer M, Bruce J, Canoll P, Hibshoosh H, Parsons R

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.

MeSH Terms
Amino Acid Sequence Animals Cell Line, Tumor Cell Survival Embryonic Stem Cells Glioblastoma/drug therapy,metabolism,pathology HEK293 Cells Humans Mice Mice, Nude Molecular Sequence Data Mutation PTEN Phosphohydrolase/chemistry,genetics,metabolism,pharmacology Peptide Chain Initiation, Translational Phosphatidylinositol 3-Kinase/metabolism Phosphorylation Proto-Oncogene Proteins c-akt/metabolism RNA, Messenger/genetics,metabolism Signal Transduction/drug effects Xenograft Model Antitumor Assays
Chemicals
RNA, Messenger Phosphatidylinositol 3-Kinase Proto-Oncogene Proteins c-akt PTEN Phosphohydrolase PTEN protein, human Pten protein, mouse
Authors & Affiliations
21 authors, click to expand affiliations / ORCID
Hopkins Benjamin D
Department of Oncological Sciences, Icahn School of Medicine at Mount Sinai, 1470 Madison Avenue, New York, NY 10029, USA.
Fine Barry
Steinbach Nicole
Dendy Meaghan
Rapp Zachary
Shaw Jacquelyn
Pappas Kyrie
Yu Jennifer S
Hodakoski Cindy
Mense Sarah
Klein Joshua
Pegno Sarah
Sulis Maria-Luisa
Goldstein Hannah
Amendolara Benjamin
Lei Liang
Maurer Matthew
Bruce Jeffrey
Canoll Peter
Hibshoosh Hanina
Parsons Ramon
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Article Info
Journal
Science (New York, N.Y.)
Abbr.
Science
ISSN
1095-9203
DOI
10.1126/science.1234907
Published
2013-07-26
Epub
2013-00-06
Pages
399-402
Language
English
Region
United States
NLM ID
0404511
PMCID
PMC3935617
Subset
IM
Grants
NINDS NIH HHS · R01 NS073610 · United States
NCI NIH HHS · 2T32 CA09503 · United States
NCI NIH HHS · R01 CA155117 · United States
NCI NIH HHS · T32 CA009503 · United States
NCI NIH HHS · CA082783 · United States
NINDS NIH HHS · R01 NS066955 · United States
NIGMS NIH HHS · T32 GM008224 · United States
NCI NIH HHS · P01 CA097403 · United States
NINDS NIH HHS · R01NS066955 · United States
NCI NIH HHS · CA097403 · United States
NCI NIH HHS · R01 CA082783 · United States
Corrections
CommentIn
PMID: 23822982
CommentIn
PMID: 23888029
External Links
PubMed source DOI: 10.1126/science.1234907 PMC Full Text View journal details
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