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The Journal of Immunology, Vol 144, Issue 9 3602-3610, Copyright © 1990 by American Association of Immunologists
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G Nunez, L London, D Hockenbery, M Alexander, JP McKearn and SJ Korsmeyer
Howard Hughes Medical Institute, Washington University School of Medicine, St. Louis, MO 63110.
The t(14;18) of human follicular B cell lymphoma translocates the Bcl-2 gene into the Ig H chain locus and markedly deregulates Bcl-2 expression. We sought to determine if Bcl-2 could be directly implicated in a growth-factor pathway. Consequently, we introduced a retrovirus containing the murine Bcl-2 gene (N2-M-Bcl-2) or the parental retrovirus (N2) into a series of factor-dependent hemopoietic cell lines. Overexpressed Bcl-2 resulted in no long term IL-2, IL-3, or IL-6 independent clones, indicating that Bcl-2 could not spare the need for a specific ligand-receptor interaction. However, Bcl-2 did extend the short term survival of IL-3-dependent cell lines after factor deprivation. Although viable, IL-3-deprived pro B lymphocytes (FL5.12) bearing N2-M-Bcl-2 were in Go, and deregulated Bcl-2 did not obviously influence cell-cycle progression. Bcl-2 predominant effects were to delay the onset of cell death and to modestly augment viable cell growth in the first 48 h after IL-3 deprivation. This death sparing was associated with increased levels of Bcl-2 RNA and protein in factor- deprived cells possessing N2-M-Bcl-2. This result was not restricted to prolymphocytes because an IL-3-dependent mast cell line (32D) as well as a promyeloid line (FDC-P1) demonstrated the same response to Bcl-2. Moreover, the effect was not limited to the IL-3/IL-3R signal transduction pathway in that promyeloid cells maintained in granulocyte- macrophage-CSF or IL-4 displayed a similar response. Yet, Bcl-2- enhanced cell survival was not universal as an IL-2-dependent T cell line, and an IL-6-dependent myeloma line demonstrated no consistent effect upon IL withdrawal. Thus, Bcl-2 appears to interfere with cell death but in a cell type and/or factor-restricted fashion.
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N. Shirafuji, S. Takahashi, S. Matsuda, and S. Asano Mitochondrial Antisense RNA for Cytochrome C Oxidase (MARCO) Can Induce Morphologic Changes and Cell Death in Human Hematopoietic Cell Lines Blood, December 1, 1997; 90(11): 4567 - 4577. [Abstract] [Full Text] [PDF] |
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A. T. Look Oncogenic Transcription Factors in the Human Acute Leukemias Science, November 7, 1997; 278(5340): 1059 - 1064. [Abstract] [Full Text] |
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V. Lacronique, P. Varlet, P. Mayeux, A. Porteu, S. Gisselbrecht, A. Kahn, and C. Lacombe Bcl-2 Targeted Overexpression Into the Erythroid Lineage of Transgenic Mice Delays But Does Not Prevent the Apoptosis of Erythropoietin-Deprived Erythroid Progenitors Blood, October 15, 1997; 90(8): 3050 - 3056. [Abstract] [Full Text] [PDF] |
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Z. Songyang, D. Baltimore, L. C. Cantley, D. R. Kaplan, and T. F. Franke Interleukin 3-dependent survival by the Akt protein kinase PNAS, October 14, 1997; 94(21): 11345 - 11350. [Abstract] [Full Text] [PDF] |
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G. F. Erickson Defining Apoptosis: Players and Systems Reproductive Sciences, September 1, 1997; 4(5): 219 - 228. [Abstract] [PDF] |
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X.-J. Tao, K. I. Tilly, D. V. Maravei, J. L. Shifren, S. Krajewski, J. C. Reed, J. L. Tilly, and K. B. Isaacson Differential Expression of Members of the bcl-2 Gene Family in Proliferative and Secretory Human Endometrium: Glandular Epithelial Cell Apoptosis Is Associated with Increased Expression of bax J. Clin. Endocrinol. Metab., August 1, 1997; 82(8): 2738 - 2746. [Abstract] [Full Text] [PDF] |
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P. L. Simonian, D. A.M. Grillot, and G. Nunez Bcl-2 and Bcl-XL Can Differentially Block Chemotherapy-Induced Cell Death Blood, August 1, 1997; 90(3): 1208 - 1216. [Abstract] [Full Text] [PDF] |
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P. A. Gregoli and M. C. Bondurant The Roles of Bcl-XL and Apopain in the Control of Erythropoiesis by Erythropoietin Blood, July 15, 1997; 90(2): 630 - 640. [Abstract] [Full Text] [PDF] |
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C. V. Clevenger, K. Thickman, W. Ngo, W.-P. Chang, S. Takayama, and J. C. Reed Role of Bag-1 in the Survival and Proliferation of the Cytokine-Dependent Lymphocyte Lines, Ba/F3 and Nb2 Mol. Endocrinol., May 1, 1997; 11(5): 608 - 618. [Abstract] [Full Text] |
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C. Sanz, A. Benito, M. Silva, B. Albella, C. Richard, J. C. Segovia, A. Insunza, J. A. Bueren, and J. L. Fernandez-Luna The Expression of Bcl-x Is Downregulated During Differentiation of Human Hematopoietic Progenitor Cells Along the Granulocyte But Not the Monocyte/Macrophage Lineage Blood, May 1, 1997; 89(9): 3199 - 3204. [Abstract] [Full Text] [PDF] |
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L. M. Osorio, A. De Santiago, M. Aguilar-SantelisesHa, k. Mellstedt, and M. Jondal CD6 Ligation Modulates the Bcl-2/Bax Ratio and Protects Chronic Lymphocytic Leukemia B Cells From Apoptosis Induced by Anti-IgM Blood, April 15, 1997; 89(8): 2833 - 2841. [Abstract] [Full Text] [PDF] |
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H. W. Findley, L. Gu, A. M. Yeager, and M. Zhou Expression and Regulation of Bcl-2, Bcl-xl, and Bax Correlate With p53 Status and Sensitivity to Apoptosis in Childhood Acute Lymphoblastic Leukemia Blood, April 15, 1997; 89(8): 2986 - 2993. [Abstract] [Full Text] [PDF] |
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V. N. Ivanov and V. N. Ivanov Transcription Factor Activation during Signal-induced Apoptosis of Immature CD4+CD8+ Thymocytes. A PROTECTIVE ROLE OF c-Fos J. Biol. Chem., March 28, 1997; 272(13): 8558 - 8566. [Abstract] [Full Text] [PDF] |
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P. Zhou, L. Qian, K. M. Kozopas, and R. W. Craig Mcl-1, a Bcl-2 Family Member, Delays the Death of Hematopoietic Cells Under a Variety of Apoptosis-Inducing Conditions Blood, January 15, 1997; 89(2): 630 - 643. [Abstract] [Full Text] [PDF] |
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H. Matsuo, T. Maruo, and T. Samoto Increased Expression of Bcl-2 Protein in Human Uterine Leiomyoma and Its Up-Regulation by Progesterone J. Clin. Endocrinol. Metab., January 1, 1997; 82(1): 293 - 299. [Abstract] [Full Text] [PDF] |
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P. L. Simonian, D. A.M. Grillot, D. W. Andrews, B. Leber, and G. Nunez Bax Homodimerization Is Not Required for Bax to Accelerate Chemotherapy-induced Cell Death J. Biol. Chem., December 13, 1996; 271(50): 32073 - 32077. [Abstract] [Full Text] [PDF] |
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K Wang, X M Yin, D T Chao, C L Milliman, and S J Korsmeyer BID: a novel BH3 domain-only death agonist. Genes & Dev., November 15, 1996; 10(22): 2859 - 2869. [Abstract] [PDF] |
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E. D. Bullock and E. M. Johnson Jr. Nerve Growth Factor Induces the Expression of Certain Cytokine Genes and bcl-2 in Mast Cells. POTENTIAL ROLE IN SURVIVAL PROMOTION J. Biol. Chem., November 1, 1996; 271(44): 27500 - 27508. [Abstract] [Full Text] [PDF] |
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A. Srinivasan, L. M. Foster, M.-P. Testa, T. Ord, R. W. Keane, D. E. Bredesen, and C. Kayalar Bcl-2 Expression in Neural Cells Blocks Activation of ICE/CED-3 Family Proteases during Apoptosis J. Neurosci., September 15, 1996; 16(18): 5654 - 5660. [Abstract] [Full Text] [PDF] |
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P. L. Simonian, D. A.M. Grillot, R. Merino, and G. Nunez Bax Can Antagonize Bcl-XL during Etoposide and Cisplatin-induced Cell Death Independently of Its Heterodimerization with Bcl-XL J. Biol. Chem., September 13, 1996; 271(37): 22764 - 22772. [Abstract] [Full Text] [PDF] |
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S. L. Gaffen, S. Y. Lai, M. Ha, X. Liu, L. Hennighausen, W. C. Greene, and M. A. Goldsmith Distinct Tyrosine Residues within the Interleukin-2 Receptor beta Chain Drive Signal Transduction Specificity, Redundancy, and Diversity J. Biol. Chem., August 30, 1996; 271(35): 21381 - 21390. [Abstract] [Full Text] [PDF] |
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D. E. Bredesen REVIEW {blacksquare} : Keeping Neurons Alive: The Molecular Control of Apoptosis (Part II Neuroscientist, July 1, 1996; 2(4): 211 - 216. [PDF] |
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N. Shiraiwa, N. Inohara, S. Okada, M. Yuzaki, S.-i. Shoji, and S. Ohta An Additional Form of Rat Bcl-x, Bcl-xbeta , Generated by an Unspliced RNA, Promotes Apoptosis in Promyeloid Cells J. Biol. Chem., May 31, 1996; 271(22): 13258 - 13265. [Abstract] [Full Text] [PDF] |
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W. Meikrantz and R. Schlegel Suppression of Apoptosis by Dominant Negative Mutants of Cyclin-dependent Protein Kinases J. Biol. Chem., April 26, 1996; 271(17): 10205 - 10209. [Abstract] [Full Text] [PDF] |
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S Shaham and H R Horvitz Developing Caenorhabditis elegans neurons may contain both cell-death protective and killer activities. Genes & Dev., March 1, 1996; 10(5): 578 - 591. [Abstract] [PDF] |
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G Middleton, G Nunez, and A. Davies Bax promotes neuronal survival and antagonises the survival effects of neurotrophic factors Development, January 2, 1996; 122(2): 695 - 701. [Abstract] [PDF] |
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S. Shankar, A. Kavanaugh-Black, S. Kamath, and A. M. Chakrabarty Characterization of a Phosphoprotein Phosphatase for the Phosphorylated Form of Nucleoside-diphosphate Kinase from Pseudomonas aeruginosa J. Biol. Chem., November 24, 1995; 270(47): 28246 - 28250. [Abstract] [Full Text] [PDF] |
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C. R. J. Morales-Ducret, M. v. d. Rijn, and B. R. Smoller bcl-2 Expression in Melanocytic Nevi: Insights Into the Biology of Dermal Maturation Arch Dermatol, August 1, 1995; 131(8): 915 - 918. [Abstract] [PDF] |
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