Involvement of the NF-kappaB pathway in the transforming properties of the TEL-Jak2 leukemogenic fusion protein

FEBS Lett. 2001 May 25;497(2-3):148-52. doi: 10.1016/s0014-5793(01)02452-8.

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

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Division / drug effects
  • Cell Line, Transformed
  • Cell Survival / drug effects
  • Cell Transformation, Neoplastic / metabolism*
  • DNA / metabolism
  • DNA-Binding Proteins / metabolism
  • Enzyme Inhibitors / pharmacology
  • I-kappa B Proteins*
  • Interleukin-3 / pharmacology
  • Leukemia / etiology
  • Leukemia / metabolism*
  • MAP Kinase Signaling System / drug effects
  • Mice
  • Mitogen-Activated Protein Kinases / antagonists & inhibitors
  • NF-KappaB Inhibitor alpha
  • NF-kappa B / antagonists & inhibitors
  • NF-kappa B / metabolism*
  • Oncogene Proteins, Fusion / metabolism*
  • Oncogene Proteins, Fusion / pharmacology
  • Phosphatidylinositol 3-Kinases / metabolism
  • Phosphorylation / drug effects
  • Protein Serine-Threonine Kinases*
  • Protein-Tyrosine Kinases
  • Proto-Oncogene Proteins / metabolism
  • Proto-Oncogene Proteins c-akt
  • Recombinant Proteins / pharmacology
  • Signal Transduction / drug effects
  • p38 Mitogen-Activated Protein Kinases

Substances

  • DNA-Binding Proteins
  • Enzyme Inhibitors
  • I-kappa B Proteins
  • Interleukin-3
  • NF-kappa B
  • NFKBIA protein, human
  • Nfkbia protein, mouse
  • Oncogene Proteins, Fusion
  • Proto-Oncogene Proteins
  • Recombinant Proteins
  • TEL-ABL fusion protein, human
  • TEL-JAK2 fusion protein, human
  • TEL-JAK2 fusion protein, mouse
  • NF-KappaB Inhibitor alpha
  • DNA
  • Protein-Tyrosine Kinases
  • Protein Serine-Threonine Kinases
  • Proto-Oncogene Proteins c-akt
  • Mitogen-Activated Protein Kinases
  • p38 Mitogen-Activated Protein Kinases