Involvement of the NF-kappaB pathway in the transforming properties of the TEL-Jak2 leukemogenic fusion protein.
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.
Santos
S C
SC
Institut Cochin de Génétique Moléculaire (ICGM), INSERM U363, Paris, France.
Monni
R
R
Bouchaert
I
I
Bernard
O
O
Gisselbrecht
S
S
Gouilleux
F
F
Penard-Lacronique
V
V
D000818:Animals; D002455:Cell Division / Q000187:drug effects; D002461:Cell Line, Transformed; D002470:Cell Survival / Q000187:drug effects; D002471:Cell Transformation, Neoplastic / Q000378:metabolism*; D004247:DNA / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D020672:I-kappa B Proteins; D007377:Interleukin-3 / Q000494:pharmacology; D007938:Leukemia / Q000209:etiology / Q000378:metabolism*; D020935:MAP Kinase Signaling System / Q000187:drug effects; D051379:Mice; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism*; D015514:Oncogene Proteins, Fusion / Q000378:metabolism* / Q000494:pharmacology; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D017346:Protein Serine-Threonine Kinases; D011505:Protein-Tyrosine Kinases; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt; D011994:Recombinant Proteins / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects; D048051:p38 Mitogen-Activated Protein Kinases; D000097764:ETS Translocation Variant 6 Protein; D053614:Janus Kinase 2
D004247:DNA; D004268:DNA-Binding Proteins; D004791:Enzyme Inhibitors; D020672:I-kappa B Proteins; D007377:Interleukin-3; D020928:Mitogen-Activated Protein Kinases; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B; D015514:Oncogene Proteins, Fusion; D019869:Phosphatidylinositol 3-Kinases; D017346:Protein Serine-Threonine Kinases; D011505:Protein-Tyrosine Kinases; D011518:Proto-Oncogene Proteins; D051057:Proto-Oncogene Proteins c-akt; D011994:Recombinant Proteins; D048051:p38 Mitogen-Activated Protein Kinases; C000606204:NFKBIA protein, human; C000606205:Nfkbia protein, mouse; C426234:TEL-ABL fusion protein, human; D000097764:ETS Translocation Variant 6 Protein; C108603:TEL-JAK2 fusion protein, human; D053614:Janus Kinase 2; C491568:TEL-JAK2 fusion protein, mouse