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Articles
by
Zhengfan Jiang |
Total Records (
1 ) for
Zhengfan Jiang |
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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
and
Xiaoxia Li
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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. |
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