|Budget Amount *help
¥3,200,000 (Direct Cost : ¥3,200,000)
Fiscal Year 1998 : ¥1,100,000 (Direct Cost : ¥1,100,000)
Fiscal Year 1997 : ¥2,100,000 (Direct Cost : ¥2,100,000)
1. We demonstrated that TRAF2 and TRAF5 interact with CD27 and CD3O, and are involved in NF-kappaB activation by these receptors. We also determined the binding domain of CD27 and CD3O for TRAF2 and TRAF5.
2. Recently, NF-kappaB kinase (NIK) was identified and has been shown to activate two subunits of the 1kappaB kinase complex, IKKalpha and IKKbeta, both of which directly phosphorylate IkappaBs. We demonstrated that while NIK activates IKKalpha and IKK3b comparably, MEKKI preferentially activates IKKbeta.
3. We showed that upon TNF treatment, TRAF2 interacts with apoptosis-regulating kinase 1 (ASK 1) and ASK1 is essential for TRAF2-mediated TNK/SAPK activation.
4. To determined the function of TRAF5 in vivo, we generated TRAF5-deficient mice. Despite of no defect of TNF-, CD27-, or CD4O-mediated activation of NF-kappaB or JNK/SAPK in TRAF5-deficient mice, CD4O- and CD27-mediated lymphocyte activation were impaired. These results suggest that a novel function of TRAF5, which is independent on activation of NF-kappaB or JNK/SAPK.