Pellino 3b negatively regulates interleukin-1-induced TAK1-dependent NFκB activation

Hui Xiao, Wen Qian, Kirk Staschke, Youcun Qian, Grace Cui, Li Deng, Mariam Ehsani, Xiliang Wang, Yue Wei Qian, Zhijian J. Chen, Raymond Gilmour, Zhengfan Jiang, Xiaoxia Li

Research output: Contribution to journalArticlepeer-review

39 Scopus citations


IL-1 receptor-associated kinase (IRAK) is phosphorylated, ubiquitinated, and degraded upon interleukin-1 (IL-1) stimulation. In this study, we showed that IRAK can be ubiquitinated through both Lys-48- and Lys-63-linked polyubiquitin chains upon IL-1 induction. Pellino 3b is the RING-like motif ubiquitin protein ligase that promotes the Lys-63-linked polyubiquitination on IRAK. Pellino 3b-mediated Lys-63-linked IRAK polyubiquitination competed with Lys-48-linked IRAK polyubiquitination for the same ubiquitination site, Lys-134 of IRAK, thereby blocking IL-1-induced IRAK degradation. Importantly, the negative impact of Pellino 3b on IL-1-induced IRAK degradation correlated with the inhibitory effect of Pellino 3b on the IL-1-induced TAK1-dependent pathway, suggesting that a positive role of IRAK degradation in IL-1 induced TAK1 activation. Taken together, our results suggest that Pellino 3b acts as a negative regulator for IL-1 signaling by regulating IRAK degradation through its ubiquitin protein ligase activity.

Original languageEnglish (US)
Pages (from-to)14654-14664
Number of pages11
JournalJournal of Biological Chemistry
Issue number21
StatePublished - May 23 2008

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology


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