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From Mammalian Cell Genetics, Biotechnology Research
Institute, National Research Council of Canada, Montreal, Quebec H4P
2R2, Canada and ¶ Department of Medicine, McGill University,
Montreal, Quebec H3G 1A4, Canada
PTEN is a tumor suppressor that primarily
dephosphorylates phosphatidylinositol 3,4,5-trisphosphate to
down-regulate the phosphoinositide3-kinase/Akt signaling pathway.
Although the cellular functionsof PTEN as a tumor suppressor have been
well characterized, themechanism by which PTEN activity is modulated
by other signalmolecules in vivo remains poorly
understood. In searching forpotential PTEN modulators through
protein-protein interaction,we identified the major vault protein
(MVP) as a dominant PTEN-bindingprotein in a yeast two-hybrid screen.
MVP is the major structuralcomponent of vault, the largest
intracellular ribonucleoproteinparticle. Co-immunoprecipitation
confirmed the interaction betweenPTEN and MVP in transfected mammalian
cells. More importantly,we found that a significant portion of
endogenous PTEN associateswith vault particles in human HeLa cells.
Deletion mutation analysisdemonstrated that MVP binds to the C2 domain
of PTEN and thatPTEN interacts with MVP through its EF
hand-like motif. Furthermore,the in vitro binding
experiments revealed that the interactionof PTEN with MVP is
Ca2+-dependent.
Phospholipid-Binding Protein EhC2A Mediates Calcium-Dependent Translocation of Transcription Factor URE3-BP to the Plasma Membrane of Entamoeba histolytica.
H. Moreno, A. S. Linford, C. A. Gilchrist, and W. A. Petri Jr. (2010)
Eukaryot. Cell
9, 695-704
|Abstract »|Full Text »|PDF »
Analysis of PTEN Complex Assembly and Identification of Heterogeneous Nuclear Ribonucleoprotein C as a Component of the PTEN-associated Complex.
S. Mosessian, N. K. Avliyakulov, D. J. Mulholland, P. Boontheung, J. A. Loo, and H. Wu (2009)
J. Biol. Chem.
284, 30159-30166
|Abstract »|Full Text »|PDF »
Activation of the PI3K Pathway in Cancer Through Inhibition of PTEN by Exchange Factor P-REX2a.
B. Fine, C. Hodakoski, S. Koujak, T. Su, L. H. Saal, M. Maurer, B. Hopkins, M. Keniry, M. L. Sulis, S. Mense, et al. (2009)
Science
325, 1261-1265
|Abstract »|Full Text »|PDF »
The Structure of Rat Liver Vault at 3.5 Angstrom Resolution.
H. Tanaka, K. Kato, E. Yamashita, T. Sumizawa, Y. Zhou, M. Yao, K. Iwasaki, M. Yoshimura, and T. Tsukihara (2009)
Science
323, 384-388
|Abstract »|Full Text »|PDF »
Host Resistance to Lung Infection Mediated by Major Vault Protein in Epithelial Cells.
M. P. Kowalski, A. Dubouix-Bourandy, M. Bajmoczi, D. E. Golan, T. Zaidi, Y. S. Coutinho-Sledge, M. P. Gygi, S. P. Gygi, E. A. C. Wiemer, and G. B. Pier (2007)
Science
317, 130-132
|Abstract »|Full Text »|PDF »
Nuclear Localization of PTEN Is Regulated by Ca2+ through a Tyrosil Phosphorylation-Independent Conformational Modification in Major Vault Protein.
Nuclear Localization of PTEN by a Ran-dependent Mechanism Enhances Apoptosis: Involvement of an N-Terminal Nuclear Localization Domain and Multiple Nuclear Exclusion Motifs.
A. Gil, A. Andres-Pons, E. Fernandez, M. Valiente, J. Torres, J. Cervera, and R. Pulido (2006)
Mol. Biol. Cell
17, 4002-4013
|Abstract »|Full Text »|PDF »
The major vault protein is responsive to and interferes with interferon-{gamma}-mediated STAT1 signals.
E. Steiner, K. Holzmann, C. Pirker, L. Elbling, M. Micksche, H. Sutterluty, and W. Berger (2006)
J. Cell Sci.
119, 459-469
|Abstract »|Full Text »|PDF »
Phosphatase and Tensin Homologue Deleted on Chromosome 10 (PTEN) Has Nuclear Localization Signal-Like Sequences for Nuclear Import Mediated by Major Vault Protein.
J.-H. Chung, M. E. Ginn-Pease, and C. Eng (2005)
Cancer Res.
65, 4108-4116
|Abstract »|Full Text »|PDF »
Regulation of PTEN Phosphorylation and Stability by a Tumor Suppressor Candidate Protein.
F. Okahara, H. Ikawa, Y. Kanaho, and T. Maehama (2004)
J. Biol. Chem.
279, 45300-45303
|Abstract »|Full Text »|PDF »
Phosphorylation-regulated Cleavage of the Tumor Suppressor PTEN by Caspase-3: IMPLICATIONS FOR THE CONTROL OF PROTEIN STABILITY AND PTEN-PROTEIN INTERACTIONS.
J. Torres, J. Rodriguez, M. P. Myers, M. Valiente, J. D. Graves, N. K. Tonks, and R. Pulido (2003)
J. Biol. Chem.
278, 30652-30660
|Abstract »|Full Text »|PDF »
Membrane-binding and activation mechanism of PTEN.