Cutting edge: K63-linked polyubiquitination of NEMO modulates TLR signaling and inflammation in vivo

Chang Yuan Ni, Zhao Hui Wu, William C. Florence, Vrajesh V. Parekh, Maria Pia Arrate, Steven Pierce, Brock Schweitzer, Luc Van Kaer, Sebastian Joyce, Shigeki Miyamoto, Dean W. Ballard, Eugene M. Oltz

Research output: Contribution to journalArticle

37 Scopus citations

Abstract

Transcription factor NF-κB controls the expression of multiple genes involved in immunity and inflammation. The initial activation and duration of NF-κB signaling is regulated by posttranslational modifications to IκB kinase, which earmarks inhibitors of NF-κB for degradation. Prior studies suggest that K63-linked ubiquitination of NEMO (NF-κB essential modulator), an IκB kinase regulatory subunit, is critical for NF-κB and MAPK signaling following engagement of Ag receptors. We now demonstrate that NF-κB and MAPK pathways are largely unaffected in primary cells from mice harboring a ubiquitination-defective form of NEMO, NEMO-KR. TLR- but not Ag receptor-induced cellular responses are impaired in NEMO-KR mice, which are more resistant to LPS-induced endo-toxic shock than wild-type animals. Thus, one function of NEMO ubiquitination is to fine tune innate immune responses under TLR control.

Original languageEnglish
Pages (from-to)7107-7111
Number of pages5
JournalJournal of Immunology
Volume180
Issue number11
DOIs
StatePublished - Jan 1 2008

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    Ni, C. Y., Wu, Z. H., Florence, W. C., Parekh, V. V., Arrate, M. P., Pierce, S., Schweitzer, B., Kaer, L. V., Joyce, S., Miyamoto, S., Ballard, D. W., & Oltz, E. M. (2008). Cutting edge: K63-linked polyubiquitination of NEMO modulates TLR signaling and inflammation in vivo. Journal of Immunology, 180(11), 7107-7111. https://doi.org/10.4049/jimmunol.180.11.7107