| Autor: |
J L, Poyet, S M, Srinivasula, J H, Lin, T, Fernandes-Alnemri, S, Yamaoka, P N, Tsichlis, E S, Alnemri |
| Rok vydání: |
2000 |
| Předmět: |
|
| Zdroj: |
The Journal of biological chemistry. 275(48) |
| ISSN: |
0021-9258 |
| Popis: |
To understand the mechanism of activation of the IkappaB 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 TNFalpha stimulation induces a large increase in the size of this complex, suggesting oligomerization. Substitution of the C-terminal region of IKKgamma, 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 IKKgamma or truncated IKKalpha or IKKbeta lacking their serine-cluster domains can also induce IKK and NF-kappaB activation. These data suggest that IKKgamma 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. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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