A short N-terminal sequence of PTEN controls cytoplasmic localization and is required for suppression of cell growth

G. Denning, B. Jean-Joseph, C. Prince, D. L. Durden, P. K. Vogt

Research output: Contribution to journalArticle

76 Citations (Scopus)

Abstract

Phosphatase and tensin homolog deleted on chromosome 10 (PTEN) is an important negative regulator of cell growth and a tumor suppressor. Its growth-attenuating activity is based on the dephosphorylation of phosphatidylinositol 3,4,5-trisphosphate (PIP3), an essential second messenger for the phosphoinositide 3-kinase/Akt signaling pathway. This activity may require localization of PTEN to cytoplasmic membranes. Yet PTEN can also localize to the cell nucleus where its functions remain unclear. Here we present data that define a short sequence in the N-terminal region of PTEN required for cytoplasmic localization. We will refer to this sequence as cytoplasmic localization signal (CLS). It could function as a non-canonical signal for nuclear export or as a cytoplasmic retention signal of PTEN. Mutations within the CLS induce nuclear localization and impair growth suppressive activities of PTEN while preserving lipid phosphatase activity. We propose that nuclear localization of PTEN is not compatible with plasma membrane-targeted growth suppressive functions of PTEN.

Original languageEnglish (US)
Pages (from-to)3930-3940
Number of pages11
JournalOncogene
Volume26
Issue number27
DOIs
StatePublished - Jun 7 2007

Fingerprint

Nuclear Localization Signals
Growth
Phosphoric Monoester Hydrolases
Cell Membrane
Nuclear Export Signals
Chromosomes, Human, Pair 10
1-Phosphatidylinositol 4-Kinase
Second Messenger Systems
Cell Nucleus
Lipids
Mutation
Neoplasms
phosphatidylinositol 3,4,5-triphosphate
Tensins

Keywords

  • Cytoplasmic localization signal
  • Lipid binding
  • Mutation
  • PTEN
  • Tumor suppressor

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research

Cite this

A short N-terminal sequence of PTEN controls cytoplasmic localization and is required for suppression of cell growth. / Denning, G.; Jean-Joseph, B.; Prince, C.; Durden, D. L.; Vogt, P. K.

In: Oncogene, Vol. 26, No. 27, 07.06.2007, p. 3930-3940.

Research output: Contribution to journalArticle

Denning, G. ; Jean-Joseph, B. ; Prince, C. ; Durden, D. L. ; Vogt, P. K. / A short N-terminal sequence of PTEN controls cytoplasmic localization and is required for suppression of cell growth. In: Oncogene. 2007 ; Vol. 26, No. 27. pp. 3930-3940.
@article{33386cb0ef9541e9b55688561c0a2f80,
title = "A short N-terminal sequence of PTEN controls cytoplasmic localization and is required for suppression of cell growth",
abstract = "Phosphatase and tensin homolog deleted on chromosome 10 (PTEN) is an important negative regulator of cell growth and a tumor suppressor. Its growth-attenuating activity is based on the dephosphorylation of phosphatidylinositol 3,4,5-trisphosphate (PIP3), an essential second messenger for the phosphoinositide 3-kinase/Akt signaling pathway. This activity may require localization of PTEN to cytoplasmic membranes. Yet PTEN can also localize to the cell nucleus where its functions remain unclear. Here we present data that define a short sequence in the N-terminal region of PTEN required for cytoplasmic localization. We will refer to this sequence as cytoplasmic localization signal (CLS). It could function as a non-canonical signal for nuclear export or as a cytoplasmic retention signal of PTEN. Mutations within the CLS induce nuclear localization and impair growth suppressive activities of PTEN while preserving lipid phosphatase activity. We propose that nuclear localization of PTEN is not compatible with plasma membrane-targeted growth suppressive functions of PTEN.",
keywords = "Cytoplasmic localization signal, Lipid binding, Mutation, PTEN, Tumor suppressor",
author = "G. Denning and B. Jean-Joseph and C. Prince and Durden, {D. L.} and Vogt, {P. K.}",
year = "2007",
month = "6",
day = "7",
doi = "10.1038/sj.onc.1210175",
language = "English (US)",
volume = "26",
pages = "3930--3940",
journal = "Oncogene",
issn = "0950-9232",
publisher = "Nature Publishing Group",
number = "27",

}

TY - JOUR

T1 - A short N-terminal sequence of PTEN controls cytoplasmic localization and is required for suppression of cell growth

AU - Denning, G.

AU - Jean-Joseph, B.

AU - Prince, C.

AU - Durden, D. L.

AU - Vogt, P. K.

PY - 2007/6/7

Y1 - 2007/6/7

N2 - Phosphatase and tensin homolog deleted on chromosome 10 (PTEN) is an important negative regulator of cell growth and a tumor suppressor. Its growth-attenuating activity is based on the dephosphorylation of phosphatidylinositol 3,4,5-trisphosphate (PIP3), an essential second messenger for the phosphoinositide 3-kinase/Akt signaling pathway. This activity may require localization of PTEN to cytoplasmic membranes. Yet PTEN can also localize to the cell nucleus where its functions remain unclear. Here we present data that define a short sequence in the N-terminal region of PTEN required for cytoplasmic localization. We will refer to this sequence as cytoplasmic localization signal (CLS). It could function as a non-canonical signal for nuclear export or as a cytoplasmic retention signal of PTEN. Mutations within the CLS induce nuclear localization and impair growth suppressive activities of PTEN while preserving lipid phosphatase activity. We propose that nuclear localization of PTEN is not compatible with plasma membrane-targeted growth suppressive functions of PTEN.

AB - Phosphatase and tensin homolog deleted on chromosome 10 (PTEN) is an important negative regulator of cell growth and a tumor suppressor. Its growth-attenuating activity is based on the dephosphorylation of phosphatidylinositol 3,4,5-trisphosphate (PIP3), an essential second messenger for the phosphoinositide 3-kinase/Akt signaling pathway. This activity may require localization of PTEN to cytoplasmic membranes. Yet PTEN can also localize to the cell nucleus where its functions remain unclear. Here we present data that define a short sequence in the N-terminal region of PTEN required for cytoplasmic localization. We will refer to this sequence as cytoplasmic localization signal (CLS). It could function as a non-canonical signal for nuclear export or as a cytoplasmic retention signal of PTEN. Mutations within the CLS induce nuclear localization and impair growth suppressive activities of PTEN while preserving lipid phosphatase activity. We propose that nuclear localization of PTEN is not compatible with plasma membrane-targeted growth suppressive functions of PTEN.

KW - Cytoplasmic localization signal

KW - Lipid binding

KW - Mutation

KW - PTEN

KW - Tumor suppressor

UR - http://www.scopus.com/inward/record.url?scp=34249991191&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=34249991191&partnerID=8YFLogxK

U2 - 10.1038/sj.onc.1210175

DO - 10.1038/sj.onc.1210175

M3 - Article

C2 - 17213812

AN - SCOPUS:34249991191

VL - 26

SP - 3930

EP - 3940

JO - Oncogene

JF - Oncogene

SN - 0950-9232

IS - 27

ER -