Article abstract
Nature Immunology 10, 1089 - 1095 (2009)
Published online: 6 September 2009 | doi:10.1038/ni.1777
Peli1 facilitates TRIF-dependent Toll-like receptor signaling and proinflammatory cytokine production
Mikyoung Chang1,2, Wei Jin1,2 & Shao-Cong Sun1
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 I
B kinase (IKK) and its 'downstream' target, transcription factor NF-B, but was dispensable for IKK–NF-B 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.
- Department of Immunology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
- These authors contributed equally to this work.
Correspondence to: Shao-Cong Sun1 e-mail: ssun@mdanderson.org.
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