期刊
JOURNAL OF BIOLOGICAL CHEMISTRY
卷 275, 期 48, 页码 37966-37977出版社
AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
DOI: 10.1074/jbc.M006643200
关键词
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资金
- NCI NIH HHS [CA38047, CA85421, CA78890] Funding Source: Medline
To understand the mechanism of activation of the I kappaB kinase (IKK) complex in the tumor necrosis factor (TNF) receptor 1 pathway, we examined the possibility that oligomerization of the IKK complex triggered by ligand-induced trimerization of the TNF receptor 1 complex is responsible for activation of the IKKs. Gel filtration analysis of the IKK complex revealed that TNF alpha stimulation induces a large increase in the size of this complex, suggesting oligomerization. Substitution of the C-terminal region of IKK gamma, which interacts with RIP, with a truncated DR4 lacking its cytoplasmic death domain, produced a molecule that could induce IKK and NF-kappaB activation in cells in response to TRAIL. Enforced oligomerization of the N terminus of IKK gamma or truncated IKK alpha or IKK beta lacking their serine-cluster domains can also induce IKK and NF-kappaB activation. These data suggest that IKK gamma functions as a signaling adaptor between the upstream regulators such as RIP and the IKKs and that oligomerization of the IKK complex by upstream regulators is a critical step in activation of this complex.
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