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Pellino 3b negatively regulates interleukin-1-induced TAK1-dependent NF kappaB activation.

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.

Pubmed ID: 18326498


  • Xiao H
  • Qian W
  • Staschke K
  • Qian Y
  • Cui G
  • Deng L
  • Ehsani M
  • Wang X
  • Qian YW
  • Chen ZJ
  • Gilmour R
  • Jiang Z
  • Li X


The Journal of biological chemistry

Publication Data

May 23, 2008

Associated Grants

  • Agency: NIGMS NIH HHS, Id: R01 GM 060020-06

Mesh Terms

  • Cell Line
  • Humans
  • Interleukin-1
  • Interleukin-1 Receptor-Associated Kinases
  • MAP Kinase Kinase Kinases
  • NF-kappa B
  • Protein Binding
  • Signal Transduction
  • Ubiquitin-Protein Ligases
  • Ubiquitination