title: TIFAB inhibits TIFA, TRAF-interacting protein with a forkhead-associated domain.
abstract: Tumor necrosis factor receptor-associated factor 6 (TRAF6) transduces signals that lead to activation of NFkappaB and AP-1, which is essential for cell differentiation and establishment of the immune and inflammatory systems. TRAF-interacting protein with a forkhead-associated domain (TIFA) was identified as a TRAF6-binding protein that could link IRAK-1 to TRAF6 and then activate TRAF6 upon stimulation. We report identification of a TIFA-related protein, TIFAB, that inhibits TIFA-mediated activation of NFkappaB. TIFAB does not associate with members of the TRAF family but does bind TIFA. We analyzed the effect of TIFAB expression on the TRAF6/TIFA interaction by immunoprecipitation of TRAF6 and found that TIFA coprecipitated with TRAF6 was not changed. However, when we analyzed this interaction by immunoprecipitation of TIFA, we found that TIFAB significantly increased the amount of TRAF6 coprecipitated with TIFA. These findings suggest that TIFAB inhibits the TIFA-mediated TRAF6 activation possibly by inducing a conformational change in TIFA.
authors.affiliation: Division of Cellular and Molecular Biology, Department of Cancer Biology, Institute of Medical Science, University of Tokyo, Shirokanedai, Minato-ku, Tokyo 108-8639, Japan.
authors.forename: Takayuki
authors.initials: T
authors.lastname: Matsumura
authors.forename: Kentaro
authors.initials: K
authors.lastname: Semba
authors.forename: Sakura
authors.initials: S
authors.lastname: Azuma
authors.forename: Shuntaro
authors.initials: S
authors.lastname: Ikawa
authors.forename: Jin
authors.initials: J
authors.lastname: Gohda
authors.forename: Taishin
authors.initials: T
authors.lastname: Akiyama
authors.forename: Jun-ichiro
authors.initials: J
authors.lastname: Inoue
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D015153:Blotting, Western; D002460:Cell Line; D015870:Gene Expression; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism; D011233:Precipitin Tests; D011506:Proteins / Q000037:antagonists & inhibitors*; D012333:RNA, Messenger / Q000096:biosynthesis; D018124:Receptors, Tumor Necrosis Factor / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D048029:TNF Receptor-Associated Factor 6; D014162:Transfection; D047988:Tumor Necrosis Factor Receptor-Associated Peptides and Proteins
chemical_list: D016328:NF-kappa B; D011506:Proteins; D012333:RNA, Messenger; D018124:Receptors, Tumor Necrosis Factor; D048029:TNF Receptor-Associated Factor 6; D047988:Tumor Necrosis Factor Receptor-Associated Peptides and Proteins