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Cutting edge: A cullin-5-TRAF6 interaction promotes TRAF6 polyubiquitination and lipopolysaccharide signaling
Zhu Z.1; Wang L.1; Hao R.1; Zhao B.1; Sun L.1; Ye R.D.1
2016-07-01
Source PublicationJournal of Immunology
ISSN15506606 00221767
Volume197Issue:1Pages:21-26
AbstractTNFR-associated factor (TRAF)6 integrates signals from multiple cell surface receptors for the activation of NFkB. However, the mechanism underlying LPS-induced TRAF6 signaling remains unclear. We report that cullin-5 (Cul-5), a cullin family scaffold protein, binds to TRAF6 and promotes TRAF6 polyubiquitination at Lys63 in response to LPS stimulation. A direct interaction between the C-terminal domain of Cul-5 and the TRAF-C domain of TRAF6 facilitates polyubiquitination of TRAF6. Hemizygous Cul-5 knockout is associated with improved survival of mice following LPS challenge and significant delays in the phosphorylation of p65/RelA, ERK, JNK, and p38 MAPKs in LPS-stimulated macrophages, along with a marked decrease in NF-κB activation. These findings identify Cul-5 as a signaling component that connects an LPS-activated TLR4-MyD88 complex to TRAF6 for efficient activation of NF-κB.
DOI10.4049/jimmunol.1600447
URLView the original
Language英語
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Cited Times [WOS]:9   [WOS Record]     [Related Records in WOS]
Document TypeJournal article
CollectionUniversity of Macau
Affiliation1.Shanghai Jiao Tong University
2.University of Macau
Recommended Citation
GB/T 7714
Zhu Z.,Wang L.,Hao R.,et al. Cutting edge: A cullin-5-TRAF6 interaction promotes TRAF6 polyubiquitination and lipopolysaccharide signaling[J]. Journal of Immunology,2016,197(1):21-26.
APA Zhu Z.,Wang L.,Hao R.,Zhao B.,Sun L.,&Ye R.D..(2016).Cutting edge: A cullin-5-TRAF6 interaction promotes TRAF6 polyubiquitination and lipopolysaccharide signaling.Journal of Immunology,197(1),21-26.
MLA Zhu Z.,et al."Cutting edge: A cullin-5-TRAF6 interaction promotes TRAF6 polyubiquitination and lipopolysaccharide signaling".Journal of Immunology 197.1(2016):21-26.
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