β-TrCP-Mediated IRAK1 Degradation Releases TAK1-TRAF6 from the Membrane to the Cytosol for TAK1-Dependent NF-κB Activation
Copyright policy )β-TrCP-Mediated IRAK1 Degradation Releases TAK1-TRAF6 from the Membrane to the Cytosol for TAK1-Dependent NF-κB Activation
Interleukin-1 (IL-1) receptor-associated kinase (IRAK1) is phosphorylated, ubiquitinated, and degraded upon IL-1 stimulation. IRAK1 can be ubiquitinated through both K48- and K63-linked polyubiquitin chains upon IL-1 stimulation. While the Pellino proteins have been shown to meditate K63-linked polyubiquitination on IRAK1, the E3 ligase for K48-linked ubiquitination of IRAK1 has not been identified. In this study, we report that the SCF (Skp1-Cullin1-F-box)-β-TrCP complex functions as the K48-linked ubiquitination E3 ligase for IRAK1. IL-1 stimulation induced the interaction of IRAK1 with Cullin1 and β-TrCP. Knockdown of β-TrCP1 and β-TrCP2 attenuated the K48-linked ubiquitination and degradation of IRAK1. Importantly, β-TrCP deficiency abolished the translocation TAK1-TRAF6 complex from the membrane to the cytosol, resulting in a diminishment of the IL-1-induced TAK1-dependent pathway. Taken together, these results implicate a positive role of β-TrCP-mediated IRAK1 degradation in IL-1-induced TAK1 activation.
- Cleveland Clinic United States
- Peking University China (People's Republic of)
- Chinese Academy of Sciences China (People's Republic of)
- State Key Laboratory of Protein and Plant Gene Research China (People's Republic of)
- Institut Pasteur of Shanghai China (People's Republic of)
TNF Receptor-Associated Factor 6, MAP Kinase Kinase 4, Ubiquitin-Protein Ligases, NF-kappa B, Ubiquitination, MAP Kinase Kinase Kinases, beta-Transducin Repeat-Containing Proteins, Cell Line, I-kappa B Kinase, Protein Transport, Cytosol, Interleukin-1 Receptor-Associated Kinases, Gene Knockdown Techniques, Humans, Phosphorylation, Interleukin-1
TNF Receptor-Associated Factor 6, MAP Kinase Kinase 4, Ubiquitin-Protein Ligases, NF-kappa B, Ubiquitination, MAP Kinase Kinase Kinases, beta-Transducin Repeat-Containing Proteins, Cell Line, I-kappa B Kinase, Protein Transport, Cytosol, Interleukin-1 Receptor-Associated Kinases, Gene Knockdown Techniques, Humans, Phosphorylation, Interleukin-1
citations This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).47 popularity This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.Top 10% influence This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).Top 10% impulse This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.Top 10%
Citations provided by BIP!Popularity provided by BIP!