Molecular Biology of the Cell Call for Nominations: MBC Editor-in-Chief

Home Help [Feedback] [For Subscribers] [Archive] [Search] --
QUICK SEARCH:   [advanced]


     

MBC in Press, published online ahead of print June 28, 2006
Mol. Biol. Cell 10.1091/mbc.E06-05-0380

A more recent version of this article appeared on September 1, 2006
This Article
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
E06-05-0380v1
17/9/4002    most recent
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Gil, A.
Right arrow Articles by Pulido, R.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Gil, A.
Right arrow Articles by Pulido, R.

Submitted on May 3, 2006
Revised on May 25, 2006
Accepted on June 20, 2006

Nuclear Localization of PTEN by a Ran-dependent Mechanism Enhances Apoptosis: Involvement of an N-Terminal Nuclear Localization Domain and Multiple Nuclear Exclusion Motifs

Anabel Gil, Amparo Andrés-Pons, Elena Fernández, Miguel Valiente, Josema Torres,* Javier Cervera, and Rafael Pulido

Centro de Investigación Príncipe Felipe, Valencia 46013, Spain

Monitoring Editor: John Cleveland

The targeting of the tumor suppressor PTEN protein to distinct subcellular compartments is a major regulatory mechanism of PTEN function, by controlling its access to substrates and effector proteins. Here, we investigated the molecular basis and functional consequences of PTEN nuclear/cytoplasmic distribution. PTEN accumulated in the nucleus of cells treated with apoptotic stimuli. Nuclear accumulation of PTEN was enhanced by mutations targeting motifs in distinct PTEN domains, and it was dependent on an N-terminal nuclear localization domain. Coexpression of a dominant negative Ran GTPase protein blocked PTEN accumulation in the nucleus, which was also affected by coexpression of importin {alpha} proteins. The lipid- and protein-phosphatase activity of PTEN differentially modulated PTEN nuclear accumulation. Furthermore, catalytically active nuclear PTEN enhanced cell apoptotic responses. Our findings indicate that multiple nuclear exclusion motifs and a nuclear localization domain control PTEN nuclear localization by a Ran-dependent mechanism, and suggest a proapoptotic role for PTEN in the cell nucleus.

*Present address: Keratinocyte Laboratory, Cancer Research UK, 44 Lincoln’s Inn Fields, London WCA 3PX, United Kingdom.

Address correspondence to: Rafael Pulido (rpulido{at}cipf.es)




This article has been cited by other articles:


Home page
 Hum Mol GenetHome page
G. P. Lobo, K. A. Waite, S. M. Planchon, T. Romigh, J. A. Houghton, and C. Eng
ATP modulates PTEN subcellular localization in multiple cancer cell lines
Hum. Mol. Genet., September 15, 2008; 17(18): 2877 - 2885.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
S. Bu, B. Kapanadze, T. Hsu, and M. Trojanowska
Opposite Effects of Dihydrosphingosine 1-Phosphate and Sphingosine 1-Phosphate on Transforming Growth Factor-{beta}/Smad Signaling Are Mediated through the PTEN/PPM1A-dependent Pathway
J. Biol. Chem., July 11, 2008; 283(28): 19593 - 19602.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
F. Fouladkou, T. Landry, H. Kawabe, A. Neeb, C. Lu, N. Brose, V. Stambolic, and D. Rotin
The ubiquitin ligase Nedd4-1 is dispensable for the regulation of PTEN stability and localization
PNAS, June 24, 2008; 105(25): 8585 - 8590.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Cell. Biol.Home page
C.-J. Chang, D. J. Mulholland, B. Valamehr, S. Mosessian, W. R. Sellers, and H. Wu
PTEN Nuclear Localization Is Regulated by Oxidative Stress and Mediates p53-Dependent Tumor Suppression
Mol. Cell. Biol., May 15, 2008; 28(10): 3281 - 3289.
[Abstract] [Full Text] [PDF]

Home page
 J. Cell Sci.Home page
S. M. Planchon, K. A. Waite, and C. Eng
The nuclear affairs of PTEN
J. Cell Sci., February 1, 2008; 121(3): 249 - 253.
[Abstract] [Full Text] [PDF]

Home page
 J. Cell Sci.Home page
T. Tamguney and D. Stokoe
New insights into PTEN
J. Cell Sci., December 1, 2007; 120(23): 4071 - 4079.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
J.-L. Liu, Z. Mao, T. A. LaFortune, M. M. Alonso, G. E. Gallick, J. Fueyo, and W.K. A. Yung
Cell Cycle Dependent Nuclear Export of Phosphatase and Tensin Homologue Tumor Suppressor Is Regulated by the Phosphoinositide-3-Kinase Signaling Cascade
Cancer Res., November 15, 2007; 67(22): 11054 - 11063.
[Abstract] [Full Text] [PDF]

Home page
 Sci SignalHome page
D. F. Barber, M. Alvarado-Kristensson, A. Gonzalez-Garcia, R. Pulido, and A. C. Carrera
PTEN Regulation, a Novel Function for the p85 Subunit of Phosphoinositide 3-Kinase
Sci. Signal., November 21, 2006; 2006(362): pe49 - pe49.
[Abstract] [Full Text] [PDF]


Home Help [Feedback] [For Subscribers] [Archive] [Search] --
Copyright © 2006 by The American Society for Cell Biology. Terms of copyright protection, warranties, and disclaimers.