TAB2 Is Essential for Prevention of Apoptosis in Fetal Liver but Not for Interleukin-1 Signaling

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-κB via mitogen-activated protein (MAP) kinases and IκB 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-κB p65-, IKKβ-, and NEMO/IKKγ-deficient mice. However, the IL-1-induced activation of NF-κB 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.

ACKNOWLEDGMENTS

We thank N. Okita, N. Iwami, and M. Kakihana for excellent technical assistance; E. Horita for secretarial assistance; and members of the Akira laboratory for their support. We also thank J. Miyazaki for CAG-cre Tg mice.

This work was supported in part by grants from Special Coordination Funds for Promoting Science and Technology; the Ministry of Education, Culture, Sports, Science, and Technology of Japan; the Japan Society for the Promotion of Science for Young Scientists; and the Virtual Research Institute of Aging of Nippon Boehringer Ingelheim.