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NF-kappaB activation through IKK-i-dependent I-TRAF/TANK phosphorylation
F Nomura1, T Kawai, K Nakanishi
1Department of Host Defense, Core Research for Evolutional Science and Technology of Japan Science and Technology Corporation, Research Institute for Microbial Diseases, Osaka University, 3-1 Yamada-oka, Suita, Osaka 565-0871, Japan.
Genes to Cells : Devoted to Molecular & Cellular Mechanisms
|April 12, 2000
Summary
Inducible IkappaB kinase-inhibitor (IKK-i) activates nuclear factor-kappaB (NF-kappaB) by phosphorylating I-TRAF/TANK. This phosphorylation liberates TRAF2, a key step in NF-kappaB pathway activation.
Area of Science:
- Molecular Biology
- Immunology
- Cell Signaling
Background:
- Nuclear factor-kappaB (NF-kappaB) is crucial for immune and inflammatory responses.
- NF-kappaB activation involves IkappaB phosphorylation and degradation.
- IKK-i is a newly identified kinase that activates NF-kappaB through distinct mechanisms.
Purpose of the Study:
- To identify molecules interacting with IKK-i.
- To elucidate the mechanism of NF-kappaB activation by IKK-i.
Main Methods:
- Yeast two-hybrid screening to identify IKK-i interacting proteins.
- In vitro kinase assays to determine IKK-i substrates.
- Over-expression studies to assess NF-kappaB activation.
Main Results:
- I-TRAF/TANK was identified as an IKK-i interacting protein.
- IKK-i phosphorylates I-TRAF, leading to TRAF2 liberation.
- NF-kappaB activation by IKK-i is dependent on I-TRAF phosphorylation and TRAF2 release.
Conclusions:
- NF-kappaB activation by IKK-i is mediated by I-TRAF/TANK phosphorylation.
- Subsequent TRAF2 liberation is a critical step in this signaling pathway.