title: TRAF-interacting protein with a forkhead-associated domain B (TIFAB) is a negative regulator of the TRAF6-induced cellular functions.
abstract: Tumour necrosis factor receptor-associated factor (TRAF)-interacting protein with a forkhead-associated domain (TIFA) activates TRAF6 to induce NF-kappaB activation. TIFA-related protein, TIFAB, is highly expressed in the spleen and inhibits TIFA-mediated TRAF6 activation. However, little is known about cell types that express TIFAB and its function in those cells. Here, we show that TIFAB is mainly expressed in B cells rather than T cells in the spleen and that the expression level was much higher in dendritic cells (DCs) and macrophages than that in splenic lymphocytes. TIFAB expression was downregulated when B cells, DCs or macrophages were stimulated by TRAF6-mediated proliferative or maturation signals including those emanating from CD40, sIgM and TLRs. Furthermore, microinjection experiments using NIH3T3 cells revealed that TIFAB inhibited entry into the S phase of the cell cycle. Our results suggest that TIFAB could act as a negative regulator of the TRAF6-induced cellular function such as B cell proliferation and maturation of DCs and macrophages.
authors.affiliation: Institute for Biomedical Engineering, Consolidated Research Institute for Advanced Science and Medical Care, Waseda University, Wasedatsurumaki-cho, Shinjuku-ku, Tokyo 162-0041, Japan.
authors.forename: Takayuki
authors.initials: T
authors.lastname: Matsumura
authors.forename: Junko
authors.initials: J
authors.lastname: Kawamura-Tsuzuku
authors.forename: Tadashi
authors.initials: T
authors.lastname: Yamamoto
authors.forename: Kentaro
authors.initials: K
authors.lastname: Semba
authors.forename: Jun-Ichiro
authors.initials: J
authors.lastname: Inoue
mesh_terms: D000818:Animals; D000888:Antibodies, Anti-Idiotypic; D001402:B-Lymphocytes / Q000378:metabolism*; D001854:Bone Marrow Cells; D023201:CD40 Ligand / Q000378:metabolism; D002453:Cell Cycle; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000378:metabolism*; D015536:Down-Regulation; D047908:Intracellular Signaling Peptides and Proteins; D008070:Lipopolysaccharides; D008264:Macrophages / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D008845:Microinjections; D041681:NIH 3T3 Cells; D010957:Plasmids; D011506:Proteins / Q000737:chemistry / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D013154:Spleen / Q000166:cytology / Q000378:metabolism; D013601:T-Lymphocytes / Q000378:metabolism*; D048029:TNF Receptor-Associated Factor 6 / Q000378:metabolism*; D051199:Toll-Like Receptor 7 / Q000819:agonists; D051217:Toll-Like Receptor 9 / Q000819:agonists
chemical_list: D000888:Antibodies, Anti-Idiotypic; D047908:Intracellular Signaling Peptides and Proteins; D008070:Lipopolysaccharides; D011506:Proteins; D012333:RNA, Messenger; C544759:TIFAB protein, mouse; D048029:TNF Receptor-Associated Factor 6; D051199:Toll-Like Receptor 7; D051217:Toll-Like Receptor 9; C044203:anti-IgM; C440499:lipopolysaccharide, Escherichia coli O111 B4; D023201:CD40 Ligand