Interleukin-1 (IL-1) Induces the Lys63-Linked Polyubiquitination of IL-1 Receptor-Associated Kinase 1 To Facilitate NEMO Binding and the Activation of IκBα Kinase
| Autor: | Margaret J. Stafford, Philip Cohen, Mark Windheim, Mark Peggie |
|---|---|
| Rok vydání: | 2008 |
| Předmět: |
congenital
hereditary and neonatal diseases and abnormalities IκB kinase Kidney Transfection Models Biological Cell Line Mice Ubiquitin Genes Reporter Luciferases Firefly Animals Humans skin and connective tissue diseases CHUK Molecular Biology Cells Cultured Luciferases Renilla TNF Receptor-Associated Factor 6 biology Kinase Lysine Intracellular Signaling Peptides and Proteins Ubiquitination I-Kappa-B Kinase IRAK1 Articles Cell Biology Fibroblasts Embryo Mammalian Molecular biology I-kappa B Kinase Enzyme Activation IκBα Interleukin-1 Receptor-Associated Kinases Proteasome Mutation biology.protein Interleukin-1 Protein Binding |
| Zdroj: | Molecular and Cellular Biology. 28:1783-1791 |
| ISSN: | 1098-5549 |
| DOI: | 10.1128/mcb.02380-06 |
| Popis: | Interleukin 1 (IL-1) has been reported to stimulate the polyubiquitination and disappearance of IL-1 receptor-associated kinase 1 (IRAK1) within minutes. It has been thought that the polyubiquitin chains attached to IRAK1 are linked via Lys48 of ubiquitin, leading to its destruction by the proteasome and explaining the rapid IL-1-induced disappearance of IRAK1. In this paper, we demonstrate that IL-1 stimulates the formation of K63-pUb-IRAK1 and not K48-pUb-IRAK1 and that the IL-1-induced disappearance of IRAK1 is not blocked by inhibition of the proteasome. We also show that IL-1 triggers the interaction of K63-pUb-IRAK1 with NEMO, a regulatory subunit of the IkappaBalpha kinase (IKK) complex, but not with the NEMO[D311N] mutant that cannot bind K63-pUb chains. Moreover, unlike wild-type NEMO, the NEMO[D311N] mutant was unable to restore IL-1-stimulated NF-kappaB-dependent gene transcription to NEMO-deficient cells. Our data suggest a model in which the recruitment of the NEMO-IKK complex to K63-pUb-IRAK1 and the recruitment of the TAK1 complex to TRAF6 facilitate the TAK1-catalyzed activation of IKK by the TRAF6-IRAK1 complex. |
| Databáze: | OpenAIRE |
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