TRAF-interacting Protein With a Forkhead-Associated Domain B (TIFAB) Is a Negative Regulator of the TRAF6-induced Cellular Functions

J Biochem. 2009 Sep;146(3):375-81. doi: 10.1093/jb/mvp080. Epub 2009 May 26.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Anti-Idiotypic
  • B-Lymphocytes / metabolism*
  • Bone Marrow Cells
  • CD40 Ligand / metabolism
  • Cell Cycle
  • Cells, Cultured
  • Dendritic Cells / metabolism*
  • Down-Regulation
  • Lipopolysaccharides
  • Macrophages / metabolism*
  • Mice
  • Mice, Inbred C57BL
  • Microinjections
  • NIH 3T3 Cells
  • Plasmids
  • Proteins / chemistry
  • Proteins / metabolism*
  • RNA, Messenger / metabolism
  • Spleen / cytology
  • Spleen / metabolism
  • T-Lymphocytes / metabolism*
  • TNF Receptor-Associated Factor 6 / metabolism*
  • Toll-Like Receptor 7 / agonists
  • Toll-Like Receptor 9 / agonists

Substances

  • Antibodies, Anti-Idiotypic
  • 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