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

Benjamin D. Hopkins; Barry Fine; Nicole Steinbach; Meaghan Dendy; Zachary Rapp; Jacquelyn Shaw; Kyrie Pappas; Jennifer S. Yu; Cindy Hodakoski; Sarah Mense; Joshua Klein; Sarah Pegno; Maria Luisa Sulis; Hannah Goldstein; Benjamin Amendolara; Liang Lei; Matthew Maurer; Jeffrey Bruce; Peter Canoll; Hanina Hibshoosh; Ramon Parsons

doi:10.1126/science.1234907

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

Benjamin D. Hopkins, Barry Fine, Nicole Steinbach, Meaghan Dendy, Zachary Rapp, Jacquelyn Shaw, Kyrie Pappas, Jennifer S. Yu, Cindy Hodakoski, Sarah Mense, Joshua Klein, Sarah Pegno, Maria Luisa Sulis, Hannah Goldstein, Benjamin Amendolara, Liang Lei, Matthew Maurer, Jeffrey Bruce, Peter Canoll, Hanina HibshooshRamon Parsons

Research output: Contribution to journal › Article › peer-review

269 Scopus citations

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.

Original language	English
Pages (from-to)	399-402
Number of pages	4
Journal	Science
Volume	341
Issue number	6144
DOIs	https://doi.org/10.1126/science.1234907
State	Published - 2013

Access to Document

10.1126/science.1234907

Cite this

Hopkins, B. D., Fine, B., Steinbach, N., Dendy, M., Rapp, Z., Shaw, J., Pappas, K., Yu, J. S., Hodakoski, C., Mense, S., Klein, J., Pegno, S., Sulis, M. L., Goldstein, H., Amendolara, B., Lei, L., Maurer, M., Bruce, J., Canoll, P., ... Parsons, R. (2013). A secreted PTEN phosphatase that enters cells to alter signaling and survival. Science, 341(6144), 399-402. https://doi.org/10.1126/science.1234907

@article{a5564782319347adaf0db70b58267336,

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.",

author = "Hopkins, {Benjamin D.} and Barry Fine and Nicole Steinbach and Meaghan Dendy and Zachary Rapp and Jacquelyn Shaw and Kyrie Pappas and Yu, {Jennifer S.} and Cindy Hodakoski and Sarah Mense and Joshua Klein and Sarah Pegno and Sulis, {Maria Luisa} and Hannah Goldstein and Benjamin Amendolara and Liang Lei and Matthew Maurer and Jeffrey Bruce and Peter Canoll and Hanina Hibshoosh and Ramon Parsons",

year = "2013",

doi = "10.1126/science.1234907",

language = "English",

volume = "341",

pages = "399--402",

journal = "Science",

issn = "0036-8075",

publisher = "American Association for the Advancement of Science",

number = "6144",

}

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 2013, 'A secreted PTEN phosphatase that enters cells to alter signaling and survival', Science, vol. 341, no. 6144, pp. 399-402. https://doi.org/10.1126/science.1234907

TY - JOUR

T1 - A secreted PTEN phosphatase that enters cells to alter signaling and survival

AU - Hopkins, Benjamin D.

AU - Fine, Barry

AU - Steinbach, Nicole

AU - Dendy, Meaghan

AU - Rapp, Zachary

AU - Shaw, Jacquelyn

AU - Pappas, Kyrie

AU - Yu, Jennifer S.

AU - Hodakoski, Cindy

AU - Mense, Sarah

AU - Klein, Joshua

AU - Pegno, Sarah

AU - Sulis, Maria Luisa

AU - Goldstein, Hannah

AU - Amendolara, Benjamin

AU - Lei, Liang

AU - Maurer, Matthew

AU - Bruce, Jeffrey

AU - Canoll, Peter

AU - Hibshoosh, Hanina

AU - Parsons, Ramon

PY - 2013

Y1 - 2013

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84880737776&partnerID=8YFLogxK

U2 - 10.1126/science.1234907

DO - 10.1126/science.1234907

M3 - Article

AN - SCOPUS:84880737776

SN - 0036-8075

VL - 341

SP - 399

EP - 402

JO - Science

JF - Science

IS - 6144

ER -

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

Abstract

Access to Document

Fingerprint

Cite this