BAT3 negatively regulates lipopolysaccharide-induced NF-κB signaling through TRAF6

Yeojin Lee, In Young Lee, Hee Jae Yun, Woo Sang Lee, Seong Man Kang, Ssang Goo Cho, Ji Eun Lee, Eui Ju Choi

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

TNF receptor-associated factor 6 (TRAF6) plays a critical role in NF-κB and mitogen-activated protein kinase (MAPK) signaling pathways, both of which mediate macrophage activation in response to pathogen-associated molecular patterns such as bacterial endotoxin, lipopolysaccharides (LPS). In this study, we investigated whether HLA-B associated transcript-3 (BAT3) regulates LPS-induced macrophage activation. BAT3 physically interacted with TRAF6 in macrophages, and this interaction was enhanced in the cells after LPS treatment. Furthermore, BAT3 inhibited the homo-oligomerization of TRAF6 as well as the interaction between TRAF6 and its downstream kinase transforming growth factor beta-activated kinase 1 (TAK1), thereby suppressing TRAF6-mediated signaling events. Intriguingly, TRAF6 mediated ubiquitination of BAT3 and this ubiquitination was crucial for its inhibitory effect on TRAF6-mediated signaling. Depletion of BAT3 by RNA interference resulted in enhancement of LPS-induced activation of the NF-κB signaling with increasing expression levels of pro-inflammatory cytokines. These findings suggest that BAT3 functions as the negative regulator of LPS-induced macrophage activation.

Original languageEnglish
Pages (from-to)784-790
Number of pages7
JournalBiochemical and Biophysical Research Communications
Volume478
Issue number2
DOIs
Publication statusPublished - 2016 Sep 16

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Keywords

  • BAT3
  • Lipopolysaccharides
  • NF-κB
  • TRAF6

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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