First Author | Zhu Z | Year | 2016 |
Journal | J Immunol | Volume | 197 |
Issue | 1 | Pages | 21-6 |
PubMed ID | 27233966 | Mgi Jnum | J:240203 |
Mgi Id | MGI:5882649 | Doi | 10.4049/jimmunol.1600447 |
Citation | Zhu Z, et al. (2016) Cutting Edge: A Cullin-5-TRAF6 Interaction Promotes TRAF6 Polyubiquitination and Lipopolysaccharide Signaling. J Immunol 197(1):21-6 |
abstractText | TNFR-associated factor (TRAF)6 integrates signals from multiple cell surface receptors for the activation of NF-kappaB. 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 Lys(63) 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-kappaB 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-kappaB. |