TAB2 is essential for prevention of apoptosis in fetal liver but not for interleukin-1 signaling

Mol Cell Biol. 2003 Feb;23(4):1231-8. doi: 10.1128/MCB.23.4.1231-1238.2003.

Abstract

The proinflammatory cytokine interleukin-1 (IL-1) transmits a signal via several critical cytoplasmic proteins such as MyD88, IRAKs and TRAF6. Recently, serine/threonine kinase TAK1 and TAK1 binding protein 1 and 2 (TAB1/2) have been identified as molecules involved in IL-1-induced TRAF6-mediated activation of AP-1 and NF-kappa B via mitogen-activated protein (MAP) kinases and I kappa B kinases, respectively. However, their physiological functions remain to be clarified. To elucidate their roles in vivo, we generated TAB2-deficient mice. The TAB2 deficiency was embryonic lethal due to liver degeneration and apoptosis. This phenotype was similar to that of NF-kappa B p65-, IKK beta-, and NEMO/IKK gamma-deficient mice. However, the IL-1-induced activation of NF-kappa B and MAP kinases was not impaired in TAB2-deficient embryonic fibroblasts. These findings demonstrate that TAB2 is essential for embryonic development through prevention of liver apoptosis but not for the IL-1 receptor-mediated signaling pathway.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing*
  • Animals
  • Apoptosis / genetics*
  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism*
  • Cells, Cultured
  • Fetal Death / genetics
  • Fibroblasts / drug effects
  • Fibroblasts / physiology
  • Genetic Engineering / methods
  • Inflammation / metabolism
  • Interleukin-1 / metabolism*
  • Interleukin-1 / pharmacology
  • Intracellular Signaling Peptides and Proteins*
  • Liver / embryology*
  • Liver / metabolism
  • Liver / pathology*
  • MAP Kinase Kinase Kinases / metabolism
  • Mice
  • Mice, Mutant Strains
  • Mitogen-Activated Protein Kinases / drug effects
  • Mitogen-Activated Protein Kinases / metabolism
  • NF-kappa B / drug effects
  • NF-kappa B / metabolism
  • Phosphorylation
  • Signal Transduction
  • Tumor Necrosis Factor-alpha / metabolism
  • Tumor Necrosis Factor-alpha / pharmacology

Substances

  • Adaptor Proteins, Signal Transducing
  • Carrier Proteins
  • Interleukin-1
  • Intracellular Signaling Peptides and Proteins
  • NF-kappa B
  • TAB1 protein, MAPKKK activator, vertebrate
  • Tab2 protein, mouse
  • Tumor Necrosis Factor-alpha
  • Mitogen-Activated Protein Kinases
  • MAP Kinase Kinase Kinases
  • MAP kinase kinase kinase 7