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 journalArticle

35 Citations (Scopus)

Abstract

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
Volume283
Issue number21
DOIs
StatePublished - May 23 2008

Fingerprint

Interleukin-1 Receptor-Associated Kinases
Interleukin-1
Chemical activation
Degradation
Ubiquitin-Protein Ligases
Polyubiquitin
Ubiquitination

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology

Cite this

Xiao, H., Qian, W., Staschke, K., Qian, Y., Cui, G., Deng, L., ... Li, X. (2008). Pellino 3b negatively regulates interleukin-1-induced TAK1-dependent NFκB activation. Journal of Biological Chemistry, 283(21), 14654-14664. https://doi.org/10.1074/jbc.M706931200

Pellino 3b negatively regulates interleukin-1-induced TAK1-dependent NFκB activation. / Xiao, Hui; Qian, Wen; Staschke, Kirk; Qian, Youcun; Cui, Grace; Deng, Li; Ehsani, Mariam; Wang, Xiliang; Qian, Yue Wei; Chen, Zhijian J.; Gilmour, Raymond; Jiang, Zhengfan; Li, Xiaoxia.

In: Journal of Biological Chemistry, Vol. 283, No. 21, 23.05.2008, p. 14654-14664.

Research output: Contribution to journalArticle

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 2008, 'Pellino 3b negatively regulates interleukin-1-induced TAK1-dependent NFκB activation', Journal of Biological Chemistry, vol. 283, no. 21, pp. 14654-14664. https://doi.org/10.1074/jbc.M706931200
Xiao, Hui ; Qian, Wen ; Staschke, Kirk ; Qian, Youcun ; Cui, Grace ; Deng, Li ; Ehsani, Mariam ; Wang, Xiliang ; Qian, Yue Wei ; Chen, Zhijian J. ; Gilmour, Raymond ; Jiang, Zhengfan ; Li, Xiaoxia. / Pellino 3b negatively regulates interleukin-1-induced TAK1-dependent NFκB activation. In: Journal of Biological Chemistry. 2008 ; Vol. 283, No. 21. pp. 14654-14664.
@article{5bc2727c6da242e290dcf40c2ae4260c,
title = "Pellino 3b negatively regulates interleukin-1-induced TAK1-dependent NFκB activation",
abstract = "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.",
author = "Hui Xiao and Wen Qian and Kirk Staschke and Youcun Qian and Grace Cui and Li Deng and Mariam Ehsani and Xiliang Wang and Qian, {Yue Wei} and Chen, {Zhijian J.} and Raymond Gilmour and Zhengfan Jiang and Xiaoxia Li",
year = "2008",
month = "5",
day = "23",
doi = "10.1074/jbc.M706931200",
language = "English (US)",
volume = "283",
pages = "14654--14664",
journal = "Journal of Biological Chemistry",
issn = "0021-9258",
publisher = "American Society for Biochemistry and Molecular Biology Inc.",
number = "21",

}

TY - JOUR

T1 - Pellino 3b negatively regulates interleukin-1-induced TAK1-dependent NFκB activation

AU - Xiao, Hui

AU - Qian, Wen

AU - Staschke, Kirk

AU - Qian, Youcun

AU - Cui, Grace

AU - Deng, Li

AU - Ehsani, Mariam

AU - Wang, Xiliang

AU - Qian, Yue Wei

AU - Chen, Zhijian J.

AU - Gilmour, Raymond

AU - Jiang, Zhengfan

AU - Li, Xiaoxia

PY - 2008/5/23

Y1 - 2008/5/23

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=47249131204&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=47249131204&partnerID=8YFLogxK

U2 - 10.1074/jbc.M706931200

DO - 10.1074/jbc.M706931200

M3 - Article

C2 - 18326498

AN - SCOPUS:47249131204

VL - 283

SP - 14654

EP - 14664

JO - Journal of Biological Chemistry

JF - Journal of Biological Chemistry

SN - 0021-9258

IS - 21

ER -