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Journal of Biochemistry Advance Access published online on May 26, 2009
Journal of Biochemistry, doi:10.1093/jb/mvp080
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© The authors 2009. Published by Oxford University Press on behalf of the Japanese Biochemical Society. All rights reserved.

TRAF-interacting protein with a forkhead-associated domain B (TIFAB) is a negative regulator of the TRAF6-induced cellular functions

Takayuki Matsumura1,2,3, Junko Kawamura-Tsuzuku4, Tadashi Yamamoto4, Kentaro Semba1,2,3 and Jun-ichiro Inoue3,*

1 Institute for Biomedical Engineering, Consolidated Research Institute for Advanced Science and Medical Care, Waseda University, Wasedatsurumaki-cho, Shinjuku-ku, Tokyo 162-0041, Japan; 2 Laboratory of Molecular Oncology, Department of Life Science and Medical Bio-Science, School of Science and Engineering, Waseda University, Wakamatsu-cho, Shinjuku-ku, Tokyo 162-8480, Japan; 3 Division of Cellular and Molecular Biology; and 4 Division of Oncology, Institute of Medical Science, University of Tokyo, Shirokanedai, Minato-ku, Tokyo 108-8639, Japan

*To whom correspondence should be addressed: Prof. Inoue, Jun-ichiro, Tel: +81-3-5449-5275, Fax: +81-3-5449-5421, E-mail: jun-i{at}ims.u-tokyo.ac.jp

Received March 6, 2009; Accepted May 18, 2009


  Abstract

Tumor necrosis factor receptor-associated factor (TRAF)-interacting protein with a forkhead-associated domain (TIFA) activates TRAF6 to induce NF-{kappa}B activation. TIFA-related protein, TIFAB, is highly expressed in 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 spleen and that expression level was much higher in dendritic cells (DCs) and macrophages than 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 S phase of the cell cycle. Our results suggest that TIFAB could acts as a negative regulator of the TRAF6-induced cellular function such as B cell proliferation and maturation of DCs and macrophages.

Key Words: NF-{kappa}β, TRAF, TIFA, forkhead-associated domain, cell cycle


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