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

Chang Yuan Ni, Zhaohui 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

35 Citations (Scopus)

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

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Ubiquitination
Inflammation
Phosphotransferases
Wild Animals
Post Translational Protein Processing
Septic Shock
Innate Immunity
Immunity
Transcription Factors
Gene Expression

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

Cite this

Ni, C. Y., Wu, Z., Florence, W. C., Parekh, V. V., Arrate, M. P., Pierce, S., ... 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

Cutting edge : K63-linked polyubiquitination of NEMO modulates TLR signaling and inflammation in vivo. / Ni, Chang Yuan; Wu, Zhaohui; Florence, William C.; Parekh, Vrajesh V.; Arrate, Maria Pia; Pierce, Steven; Schweitzer, Brock; Kaer, Luc Van; Joyce, Sebastian; Miyamoto, Shigeki; Ballard, Dean W.; Oltz, Eugene M.

In: Journal of Immunology, Vol. 180, No. 11, 01.01.2008, p. 7107-7111.

Research output: Contribution to journalArticle

Ni, CY, Wu, Z, Florence, WC, Parekh, VV, Arrate, MP, Pierce, S, Schweitzer, B, Kaer, LV, Joyce, S, Miyamoto, S, Ballard, DW & Oltz, EM 2008, 'Cutting edge: K63-linked polyubiquitination of NEMO modulates TLR signaling and inflammation in vivo', Journal of Immunology, vol. 180, no. 11, pp. 7107-7111. https://doi.org/10.4049/jimmunol.180.11.7107
Ni, Chang Yuan ; Wu, Zhaohui ; Florence, William C. ; Parekh, Vrajesh V. ; Arrate, Maria Pia ; Pierce, Steven ; Schweitzer, Brock ; Kaer, Luc Van ; Joyce, Sebastian ; Miyamoto, Shigeki ; Ballard, Dean W. ; Oltz, Eugene M. / Cutting edge : K63-linked polyubiquitination of NEMO modulates TLR signaling and inflammation in vivo. In: Journal of Immunology. 2008 ; Vol. 180, No. 11. pp. 7107-7111.
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