| Title | beta-TrCP-Mediated IRAK1 Degradation Releases TAK1-TRAF6 from the Membrane to the Cytosol for TAK1-Dependent NF-kappa B Activation |
| Authors | Cui, Wei Xiao, Nengming Xiao, Hui Zhou, Hao Yu, Minjia Gu, Jun Li, Xiaoxia |
| Affiliation | Peking Univ, LSC, State Key Lab Prot & Plant Gene Res, Beijing 100871, Peoples R China. Cleveland Clin Fdn, Dept Immunol, Cleveland, OH 44195 USA. Chinese Acad Sci, Inst Pasteur Shanghai, Key Lab Mol Virol & Immunol, Shanghai, Peoples R China. |
| Keywords | INTERLEUKIN-1 RECEPTOR ADAPTER PROTEIN KINASE TAK1 IL-1 PATHWAY TAB3 COMPLEX ALPHA UBIQUITINATION CATENIN |
| Issue Date | 2012 |
| Publisher | molecular and cellular biology |
| Citation | MOLECULAR AND CELLULAR BIOLOGY.2012,32,(19),3990-4000. |
| Abstract | 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)-beta-TrCP complex functions as the K48-linked ubiquitination E3 ligase for IRAK1. IL-1 stimulation induced the interaction of IRAK1 with Cullin1 and beta-TrCP. Knockdown of beta-TrCP1 and beta-TrCP2 attenuated the K48-linked ubiquitination and degradation of IRAK1. Importantly, beta-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 beta-TrCP-mediated IRAK1 degradation in IL-1-induced TAK1 activation. |
| URI | http://hdl.handle.net/20.500.11897/343217 |
| ISSN | 0270-7306 |
| DOI | 10.1128/MCB.00722-12 |
| Indexed | SCI(E) PubMed |
| Appears in Collections: | 待认领 |
