Abstract
Constitutively active tyrosine kinases are frequently expressed in various types of human leukemias as the result of chromosomal translocations. The TEL-Jak2 fusion oncoprotein possesses transforming properties in both animal and cellular models, that are tightly dependent on Stat5 activation. In the IL-3-independent TEL-Jak2-transformed Ba/F3 cells, activation of the PI-3K/Akt pathway appears essential to cell proliferation. Here we report a sustained activation of NF-kappaB factors in Ba/F3 cells, which inhibition dramatically impairs cell viability, indicating that NF-kappaB signaling exerts a major role in the anti-apoptotic activities of TEL-Jak2 oncoprotein.
Publication types
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Comparative Study
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Cell Division / drug effects
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Cell Line, Transformed
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Cell Survival / drug effects
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Cell Transformation, Neoplastic / metabolism*
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DNA / metabolism
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DNA-Binding Proteins / metabolism
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Enzyme Inhibitors / pharmacology
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I-kappa B Proteins*
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Interleukin-3 / pharmacology
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Leukemia / etiology
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Leukemia / metabolism*
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MAP Kinase Signaling System / drug effects
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Mice
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Mitogen-Activated Protein Kinases / antagonists & inhibitors
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NF-KappaB Inhibitor alpha
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NF-kappa B / antagonists & inhibitors
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NF-kappa B / metabolism*
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Oncogene Proteins, Fusion / metabolism*
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Oncogene Proteins, Fusion / pharmacology
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Phosphatidylinositol 3-Kinases / metabolism
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Phosphorylation / drug effects
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Protein Serine-Threonine Kinases*
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Protein-Tyrosine Kinases
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Proto-Oncogene Proteins / metabolism
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Proto-Oncogene Proteins c-akt
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Recombinant Proteins / pharmacology
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Signal Transduction / drug effects
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p38 Mitogen-Activated Protein Kinases
Substances
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DNA-Binding Proteins
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Enzyme Inhibitors
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I-kappa B Proteins
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Interleukin-3
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NF-kappa B
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NFKBIA protein, human
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Nfkbia protein, mouse
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Oncogene Proteins, Fusion
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Proto-Oncogene Proteins
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Recombinant Proteins
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TEL-ABL fusion protein, human
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TEL-JAK2 fusion protein, human
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TEL-JAK2 fusion protein, mouse
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NF-KappaB Inhibitor alpha
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DNA
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Protein-Tyrosine Kinases
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Protein Serine-Threonine Kinases
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Proto-Oncogene Proteins c-akt
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Mitogen-Activated Protein Kinases
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p38 Mitogen-Activated Protein Kinases