title: BAT3 negatively regulates lipopolysaccharide-induced NF-κB signaling through TRAF6.
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.
authors: Department of Life Sciences, Korea University, Seoul 136-701, South Korea.
authors: Yeojin
authors: Y
authors: Lee
authors: Department of Life Sciences, Korea University, Seoul 136-701, South Korea.
authors: In Young
authors: IY
authors: Lee
authors: Department of Life Sciences, Korea University, Seoul 136-701, South Korea.
authors: Hee Jae
authors: HJ
authors: Yun
authors: Department of Life Sciences, Korea University, Seoul 136-701, South Korea.
authors: Woo Sang
authors: WS
authors: Lee
authors: Department of Life Sciences, Korea University, Seoul 136-701, South Korea.
authors: Seongman
authors: S
authors: Kang
authors: Department of Animal Biotechnology and Incurable Disease Animal Model and Stem Cell Institute (IDASI), Konkuk University, Seoul 143-701, South Korea.
authors: Ssang-Goo
authors: SG
authors: Cho
authors: Department of Health Sciences and Technology, Samsung Advanced Institute for Health Sciences & Technology (SAIHST), Sungkyunkwan University, South Korea; Samsung Genome Institute (SGI), Samsung Medical Center, Seoul 135-710, South Korea. Electronic address: jieun.lee@skku.edu.
authors: Ji Eun
authors: JE
authors: Lee
authors: Department of Life Sciences, Korea University, Seoul 136-701, South Korea. Electronic address: ejchoi@korea.ac.kr.
authors: Eui-Ju
authors: EJ
authors: Choi
mesh_terms: D000818:Animals; D002460:Cell Line; D016207:Cytokines / Q000235:genetics / Q000276:immunology; D005786:Gene Expression Regulation; D057809:HEK293 Cells; D006801:Humans; D008070:Lipopolysaccharides / Q000494:pharmacology*; D020930:MAP Kinase Kinase Kinases / Q000235:genetics / Q000276:immunology; D008262:Macrophage Activation / Q000187:drug effects*; D008264:Macrophages / Q000166:cytology / Q000187:drug effects* / Q000276:immunology; D051379:Mice; D018832:Molecular Chaperones / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000276:immunology; D016328:NF-kappa B / Q000235:genetics* / Q000276:immunology; D009687:Nuclear Proteins / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000276:immunology; D011485:Protein Binding; D055503:Protein Multimerization; D055550:Protein Stability; D059748:Proteolysis; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D048029:TNF Receptor-Associated Factor 6 / Q000235:genetics* / Q000276:immunology; D054875:Ubiquitination; D000099151:MAP Kinase Kinase Kinase 7
chemical_list: D016207:Cytokines; D008070:Lipopolysaccharides; D020930:MAP Kinase Kinase Kinases; D018832:Molecular Chaperones; D016328:NF-kappa B; D009687:Nuclear Proteins; D034741:RNA, Small Interfering; D048029:TNF Receptor-Associated Factor 6; D000099151:MAP Kinase Kinase Kinase 7; C484266:Bag6 protein, mouse
keywords: BAT3; Lipopolysaccharides; NF-κB; TRAF6