Peli1 Facilitates TRIF-dependent Toll-like Receptor Signaling and Proinflammatory Cytokine Production

Overview

Journal Nat Immunol

Date 2009 Sep 8

PMID 19734906

Citations 146

Authors

Mikyoung Chang

Wei Jin

Shao-Cong Sun

Affiliations

Soon will be listed here.

Abstract

Toll-like receptors (TLRs) are pivotal in innate immunity and inflammation. Here we show that genetic deficiency in Peli1, an E3 ubiquitin ligase, attenuated the induction of proinflammatory cytokines by ligands of TLR3 and TLR4 and rendered mice resistant to septic shock. Peli1 was required for TLR3-induced activation of IkappaB kinase (IKK) and its 'downstream' target, transcription factor NF-kappaB, but was dispensable for IKK-NF-kappaB activation induced by several other TLRs and the interleukin 1 (IL-1) receptor. Notably, Peli1 bound to and ubiquitinated RIP1, a signaling molecule that mediates IKK activation induced by the TLR3 and TLR4 adaptor TRIF. Our findings suggest that Peli1 is a ubiquitin ligase needed for the transmission of TRIF-dependent TLR signals.

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