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Science 14 August 1998:
Vol. 281. no. 5379, pp. 998 - 1001
DOI: 10.1126/science.281.5379.998
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Reports

IEX-1L, an Apoptosis Inhibitor Involved in NF-kappa B-Mediated Cell Survival

Mei X. Wu, * Zhaohui Ao, K. V. S. Prasad, Ruilian Wu, Stuart F. Schlossman

Transcription factors of the nuclear factor-kappa B/rel (NF-kappa B) family may be important in cell survival by regulating unidentified, anti-apoptotic genes. One such gene that protects cells from apoptosis induced by Fas or tumor necrosis factor type alpha  (TNF), IEX-1L, is described here. Its transcription induced by TNF was decreased in cells with defective NF-kappa B activation, rendering them sensitive to TNF-induced apoptosis, which was abolished by transfection with IEX-1L. In support, overexpression of antisense IEX-1L partially blocked TNF-induced expression of IEX-1L and sensitized normal cells to killing. This study demonstrates a key role of IEX-1L in cellular resistance to TNF-induced apoptosis.

Division of Tumor Immunology, Dana-Farber Cancer Institute, and the Department of Medicine, Harvard Medical School, Boston, MA 02115, USA.
*   To whom correspondence should be addressed.

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J. Biol. Chem. 274, 28916-28921
   Abstract »    Full Text »    PDF »
Induction of Bcl-xL Expression by Human T-Cell Leukemia Virus Type 1 Tax through NF-kappa B in Apoptosis-Resistant T-Cell Transfectants with Tax.
T. Tsukahara, M. Kannagi, T. Ohashi, H. Kato, M. Arai, G. Nunez, Y. Iwanaga, N. Yamamoto, K. Ohtani, M. Nakamura, et al. (1999)
J. Virol. 73, 7981-7987
   Abstract »    Full Text »    PDF »
Cleavage of the death domain kinase RIP by Caspase-8 prompts TNF-induced apoptosis.
Y. Lin, A. Devin, Y. Rodriguez, and Z.-g. Liu (1999)
Genes & Dev. 13, 2514-2526
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NF-kappa B Induces Expression of the Bcl-2 Homologue A1/Bfl-1 To Preferentially Suppress Chemotherapy-Induced Apoptosis.
C.-Y. Wang, D. C. Guttridge, M. W. Mayo, and A. S. Baldwin Jr. (1999)
Mol. Cell. Biol. 19, 5923-5929
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Experimental Autoimmune Encephalomyelitis in NF-{kappa}B- Deficient Mice: Roles of NF-{kappa}B in the Activation and Differentiation of Autoreactive T Cells.
B. Hilliard, E. B. Samoilova, T.-S. T. Liu, A. Rostami, and Y. Chen (1999)
J. Immunol. 163, 2937-2943
   Abstract »    Full Text »    PDF »
TRAIL Death Pathway Expression and Induction in Thyroid Follicular Cells.
J. D. Bretz, M. Rymaszewski, P. L. Arscott, A. Myc, K. B. Ain, N. W. Thompson, and J. R. Baker Jr. (1999)
J. Biol. Chem. 274, 23627-23632
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NF-kappa B-mediated up-regulation of Bcl-x and Bfl-1/A1 is required for CD40 survival signaling in B lymphocytes.
H. H. Lee, H. Dadgostar, Q. Cheng, J. Shu, and G. Cheng (1999)
PNAS 96, 9136-9141
   Abstract »    Full Text »    PDF »
Intrastriatal Dopamine Injection Induces Apoptosis Through Oxidation-Involved Activation of Transcription Factors AP-1 and NF-kappa B in Rats.
Y. Luo, A. Hattori, J. Munoz, Z.-H. Qin, and G. S. Roth (1999)
Mol. Pharmacol. 56, 254-264
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Apoptosis Promotes a Caspase-induced Amino-terminal Truncation of Ikappa Balpha That Functions as a Stable Inhibitor of NF-kappa B.
J. Y. Reuther and A. S. Baldwin Jr. (1999)
J. Biol. Chem. 274, 20664-20670
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Inactivation of the Inhibitory kappa B Protein Kinase/Nuclear Factor kappa B Pathway by Par-4 Expression Potentiates Tumor Necrosis Factor alpha -induced Apoptosis.
M. T. Diaz-Meco, M.-J. Lallena, A. Monjas, S. Frutos, and J. Moscat (1999)
J. Biol. Chem. 274, 19606-19612
   Abstract »    Full Text »    PDF »
Bridging the Gap: Composition, Regulation, and Physiological Function of the Ikappa B Kinase Complex.
E. Zandi and M. Karin (1999)
Mol. Cell. Biol. 19, 4547-4551
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Expression of a Dominant-Negative Mutant Inhibitor-{{kappa}}B{{alpha}} of Nuclear Factor-{{kappa}}B in Human Head and Neck Squamous Cell Carcinoma Inhibits Survival, Proinflammatory Cytokine Expression, and Tumor Growth in Vivo.
D. C. Duffey, Z. Chen, G. Dong, F. G. Ondrey, J. S. Wolf, K. Brown, U. Siebenlist, and C. Van Waes (1999)
Cancer Res. 59, 3468-3474
   Abstract »    Full Text »    PDF »
Cytokine-induced Apoptosis in Epithelial HT-29 Cells Is Independent of Nitric Oxide Formation. EVIDENCE FOR AN INTERLEUKIN-13-DRIVEN PHOSPHATIDYLINOSITOL 3-KINASE-DEPENDENT SURVIVAL MECHANISM.
K. Wright, G. Kolios, J. Westwick, and S. G. Ward (1999)
J. Biol. Chem. 274, 17193-17201
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Host Cell Death due to Enteropathogenic Escherichia coli Has Features of Apoptosis.
J. K. Crane, S. Majumdar, and D. F. Pickhardt III (1999)
Infect. Immun. 67, 2575-2584
   Abstract »    Full Text »    PDF »
Transcriptional Cross Talk between NF-kappa B and p53.
G. A. Webster and N. D. Perkins (1999)
Mol. Cell. Biol. 19, 3485-3495
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Nuclear Factor {{kappa}}B Cooperates with c-Myc in Promoting Murine Hepatocyte Survival in a Manner Independentof p53 Tumor Suppressor Function.
R. E. Bellas and G. E. Sonenshein (1999)
Cell Growth Differ. 10, 287-294
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The Role of Antiapoptotic Bcl-2 Family Members in Endothelial Apoptosis Elucidated with Antisense Oligonucleotides.
E. J. Ackermann, J. K. Taylor, R. Narayana, and C. F. Bennett (1999)
J. Biol. Chem. 274, 11245-11252
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Absence of tumor necrosis factor rescues RelA-deficient mice from embryonic lethality.
T. S. Doi, M. W. Marino, T. Takahashi, T. Yoshida, T. Sakakura, L. J. Old, and Y. Obata (1999)
PNAS 96, 2994-2999
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The prosurvival Bcl-2 homolog Bfl-1/A1 is a direct transcriptional target of NF-kappa B that blocks TNFalpha -induced apoptosis.
W.-X. Zong, L. C. Edelstein, C. Chen, J. Bash, and C. Gélinas (1999)
Genes & Dev. 13, 382-387
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Rel-dependent induction of A1 transcription is required to protect B cells from antigen receptor ligation-induced apoptosis.
R. J. Grumont, I. J. Rourke, and S. Gerondakis (1999)
Genes & Dev. 13, 400-411
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CREB-binding Protein Is a Nuclear Integrator of Nuclear Factor-kappa B and p53 Signaling.
R. Wadgaonkar, K. M. Phelps, Z. Haque, A. J. Williams, E. S. Silverman, and T. Collins (1999)
J. Biol. Chem. 274, 1879-1882
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The NF-kappa B Signaling Pathway Is Not Required for Fas Ligand Gene Induction but Mediates Protection from Activation-induced Cell Death.
I. Rivera-Walsh, M. E. Cvijic, G. Xiao, and S.-C. Sun (2000)
J. Biol. Chem. 275, 25222-25230
   Abstract »    Full Text »    PDF »


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