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Science 24 September 1999:
Vol. 285. no. 5436, pp. 2122 - 2125
DOI: 10.1126/science.285.5436.2122
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Reports

Impaired Fas Response and Autoimmunity in Pten+/- Mice

Antonio Di Cristofano, 1 Paraskevi Kotsi, 1 Yu Feng Peng, 3 Carlos Cordon-Cardo, 2 Keith B. Elkon, 3 Pier Paolo Pandolfi 1*

Inactivating mutations in the PTEN tumor suppressor gene, encoding a phosphatase, occur in three related human autosomal dominant disorders characterized by tumor susceptibility. Here it is shown that Pten heterozygous (Pten+/-) mutants develop a lethal polyclonal autoimmune disorder with features reminiscent of those observed in Fas-deficient mutants. Fas-mediated apoptosis was impaired in Pten+/- mice, and T lymphocytes from these mice show reduced activation-induced cell death and increased proliferation upon activation. Phosphatidylinositol (PI) 3-kinase inhibitors restored Fas responsiveness in Pten+/- cells. These results indicate that Pten is an essential mediator of the Fas response and a repressor of autoimmunity and thus implicate the PI 3-kinase/Akt pathway in Fas-mediated apoptosis.

1 Department of Human Genetics-Molecular Biology Program,
2 Department of Pathology, Memorial Sloan-Kettering Cancer Center, Sloan-Kettering Institute, 1275 York Avenue, New York, NY 10021, USA.
3 Hospital for Special Surgery, Cornell University Medical College, New York, NY 10021, USA.
*   To whom correspondence should be addressed. E-mail: p-pandolfi{at}ski.mskcc.org

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   Abstract »    Full Text »    PDF »
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   Abstract »    Full Text »    PDF »
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   Abstract »    Full Text »    PDF »
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   Abstract »    Full Text »    PDF »
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   Abstract »    Full Text »    PDF »
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   Abstract »    Full Text »    PDF »
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X.-P. Zhong, E. A. Hainey, B. A. Olenchock, H. Zhao, M. K. Topham, and G. A. Koretzky (2002)
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   Abstract »    Full Text »    PDF »
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   Abstract »    Full Text »    PDF »
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R. G. Jones, A. R. Elford, M. J. Parsons, L. Wu, C. M. Krawczyk, W.-C. Yeh, R. Hakem, R. Rottapel, J. R. Woodgett, and P. S. Ohashi (2002)
J. Exp. Med. 196, 335-348
   Abstract »    Full Text »    PDF »
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C. B. Knobbe, A. Merlo, and G. Reifenberger (2002)
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   Abstract »    PDF »
The Inducible Expression of the Tumor Suppressor Gene PTEN Promotes Apoptosis and Decreases Cell Size by Inhibiting the PI3K/Akt Pathway in Jurkat T Cells.
Z. Xu, D. Stokoe, L. P. Kane, and A. Weiss (2002)
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   Abstract »    Full Text »
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   Abstract »    Full Text »    PDF »
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M. A. Davies, S. J. Kim, N. U. Parikh, Z. Dong, C. D. Bucana, and G. E. Gallick (2002)
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   Abstract »    Full Text »    PDF »
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M. Butler, R. A. McKay, I. J. Popoff, W. A. Gaarde, D. Witchell, S. F. Murray, N. M. Dean, S. Bhanot, and B. P. Monia (2002)
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   Abstract »    Full Text »    PDF »
Phosphoinositide-specific Inositol Polyphosphate 5-Phosphatase IV Inhibits Akt/Protein Kinase B Phosphorylation and Leads to Apoptotic Cell Death.
M. V. Kisseleva, L. Cao, and P. W. Majerus (2002)
J. Biol. Chem. 277, 6266-6272
   Abstract »    Full Text »    PDF »
Regulation of Fas Expression by STAT3 and c-Jun Is Mediated by Phosphatidylinositol 3-Kinase-AKT Signaling.
V. N. Ivanov, M. Krasilnikov, and Z.'e. Ronai (2002)
J. Biol. Chem. 277, 4932-4944
   Abstract »    Full Text »    PDF »
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T. Suhara, H.-S. Kim, L. A. Kirshenbaum, and K. Walsh (2002)
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   Abstract »    Full Text »    PDF »
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E. Kelly, A. Won, Y. Refaeli, and L. V. Parijs (2002)
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   Abstract »    Full Text »    PDF »
PTEN controls immunoreceptor (immunoreceptor tyrosine-based activation motif) signaling and the activation of Rac.
J. S. Kim, X. Peng, P. K. De, R. L. Geahlen, and D. L. Durden (2002)
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   Abstract »    Full Text »    PDF »
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J. Biol. Chem. 276, 47563-47574
   Abstract »    Full Text »    PDF »
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Y Xu and P H Wiernik (2001)
Lupus 10, 841-850
   Abstract »    PDF »
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E. Hatano and D. A. Brenner (2001)
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   Abstract »    Full Text »    PDF »
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B. Kwabi-Addo, D. Giri, K. Schmidt, K. Podsypanina, R. Parsons, N. Greenberg, and M. Ittmann (2001)
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   Abstract »    Full Text »    PDF »
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S. Talapatra and C. B. Thompson (2001)
J. Pharmacol. Exp. Ther. 298, 873-878
   Abstract »    Full Text »
Autoimmune Diseases.
A. Davidson and B. Diamond (2001)
N. Engl. J. Med. 345, 340-350
   Full Text »    PDF »
PTEN: A Newly Identified Regulator of Neuronal Differentiation.
A. H. Ross, M. B. Lachyankar, and L. D. Recht (2001)
Neuroscientist 7, 278-281
   Abstract »    PDF »
Constitutively Activated Akt-1 Is Vital for the Survival of Human Monocyte-Differentiated Macrophages: Role of Mcl-1, Independent of Nuclear Factor (Nf)-{kappa}b, Bad, or Caspase Activation.
H. Liu, H. Perlman, L. J. Pagliari, and R. M. Pope (2001)
J. Exp. Med. 194, 113-126
   Abstract »    Full Text »    PDF »
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M. J. Parsons, R. G. Jones, M.-S. Tsao, B. Odermatt, P. S. Ohashi, and J. R. Woodgett (2001)
J. Immunol. 167, 42-48
   Abstract »    Full Text »    PDF »
Growth and Gene Expression Profile Analyses of Endometrial Cancer Cells Expressing Exogenous PTEN.
M. Matsushima-Nishiu, M. Unoki, K. Ono, T. Tsunoda, T. Minaguchi, H. Kuramoto, M. Nishida, T. Satoh, T. Tanaka, and Y. Nakamura (2001)
Cancer Res. 61, 3741-3749
   Abstract »    Full Text »
Novel vitamin D3 analog, 21-(3-methyl-3-hydroxy-butyl)-19-nor D3, that modulates cell growth, differentiation, apoptosis, cell cycle, and induction of PTEN in leukemic cells.
J.-i. Hisatake, J. O'Kelly, M. R. Uskokovic, S. Tomoyasu, and H. P. Koeffler (2001)
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   Abstract »    Full Text »    PDF »
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   Abstract »    Full Text »    PDF »
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   Abstract »    Full Text »    PDF »
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   Abstract »    Full Text »    PDF »
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   Abstract »    Full Text »
Follicle-Stimulating Hormone (FSH) Stimulates Phosphorylation and Activation of Protein Kinase B (PKB/Akt) and Serum and Glucocorticoid-Induced Kinase (Sgk): Evidence for A Kinase-Independent Signaling by FSH in Granulosa Cells.
I. J. Gonzalez-Robayna, A. E. Falender, S. Ochsner, G. L. Firestone, and J. S. Richards (2000)
Mol. Endocrinol. 14, 1283-1300
   Abstract »    Full Text »
Phosphorylation of the PTEN Tail Regulates Protein Stability and Function.
F. Vazquez, S. Ramaswamy, N. Nakamura, and W. R. Sellers (2000)
Mol. Cell. Biol. 20, 5010-5018
   Abstract »    Full Text »
High Incidence of Breast and Endometrial Neoplasia Resembling Human Cowden Syndrome in pten+/- Mice.
V. Stambolic, M.-S. Tsao, D. Macpherson, A. Suzuki, W. B. Chapman, and T. W. Mak (2000)
Cancer Res. 60, 3605-3611
   Abstract »    Full Text »
Increased phosphoinositide 3-kinase activity induces a lymphoproliferative disorder and contributes to tumor generation in vivo.
L. R.-BORLADO, C. REDONDO, B. ALVAREZ, C. JIMENEZ, L. M. CRIADO, J. FLORES, M. A. R. MARCOS, C. MARTINEZ-A, D. BALOMENOS, and A. C. CARRERA (2000)
FASEB J 14, 895-903
   Abstract »    Full Text »
A Role for Nuclear PTEN in Neuronal Differentiation.
M. B. Lachyankar, N. Sultana, C. M. Schonhoff, P. Mitra, W. Poluha, S. Lambert, P. J. Quesenberry, N. S. Litofsky, L. D. Recht, R. Nabi, et al. (2000)
J. Neurosci. 20, 1404-1413
   Abstract »    Full Text »    PDF »
The Bile Acid Taurochenodeoxycholate Activates a Phosphatidylinositol 3-Kinase-dependent Survival Signaling Cascade.
C. Rust, L. M. Karnitz, C. V. Paya, J. Moscat, R. D. Simari, and G. J. Gores (2000)
J. Biol. Chem. 275, 20210-20216
   Abstract »    Full Text »    PDF »
Phosphoinositide 3-kinase and Bruton's tyrosine kinase regulate overlapping sets of genes in B lymphocytes.
D. A. Fruman, G. Z. Ferl, S. S. An, A. C. Donahue, A. B. Satterthwaite, and O. N. Witte (2002)
PNAS 99, 359-364
   Abstract »    Full Text »    PDF »
Haploinsufficiency of the Pten tumor suppressor gene promotes prostate cancer progression.
B. Kwabi-Addo, D. Giri, K. Schmidt, K. Podsypanina, R. Parsons, N. Greenberg, and M. Ittmann (2001)
PNAS 98, 11563-11568
   Abstract »    Full Text »    PDF »
Phosphatidylinositol 3-Kinase/Akt Signaling Controls Endothelial Cell Sensitivity to Fas-Mediated Apoptosis via Regulation of FLICE-Inhibitory Protein (FLIP).
T. Suhara, T. Mano, B. E. Oliveira, and K. Walsh (2001)
Circ. Res. 89, 13-19
   Abstract »    Full Text »    PDF »


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