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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.
AuthorsTakayuki Matsumura, Junko Kawamura-Tsuzuku, Tadashi Yamamoto, Kentaro Semba, Jun-Ichiro Inoue
JournalJournal of biochemistry (J Biochem) Vol. 146 Issue 3 Pg. 375-81 (Sep 2009) ISSN: 1756-2651 [Electronic] England
PMID19470519 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Antibodies, Anti-Idiotypic
  • Intracellular Signaling Peptides and Proteins
  • Lipopolysaccharides
  • Proteins
  • RNA, Messenger
  • TIFAB protein, mouse
  • TNF Receptor-Associated Factor 6
  • Toll-Like Receptor 7
  • Toll-Like Receptor 9
  • anti-IgM
  • lipopolysaccharide, Escherichia coli O111 B4
  • CD40 Ligand
Topics
  • Animals
  • Antibodies, Anti-Idiotypic
  • B-Lymphocytes (metabolism)
  • Bone Marrow Cells
  • CD40 Ligand (metabolism)
  • Cell Cycle
  • Cells, Cultured
  • Dendritic Cells (metabolism)
  • Down-Regulation
  • Intracellular Signaling Peptides and Proteins
  • Lipopolysaccharides
  • Macrophages (metabolism)
  • Mice
  • Mice, Inbred C57BL
  • Microinjections
  • NIH 3T3 Cells
  • Plasmids
  • Proteins (chemistry, metabolism)
  • RNA, Messenger (metabolism)
  • Spleen (cytology, metabolism)
  • T-Lymphocytes (metabolism)
  • TNF Receptor-Associated Factor 6 (metabolism)
  • Toll-Like Receptor 7 (agonists)
  • Toll-Like Receptor 9 (agonists)

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