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The Journal of Biochemistry
Year: 2009  |  Volume: 146  |  Issue: 3  |  Page No.: 375 - 381

TRAF-Interacting Protein with a Forkhead-Associated Domain B (TIFAB) Is a Negative Regulator of the TRAF6-Induced Cellular Functions

T Matsumura, J Kawamura Tsuzuku, T Yamamoto, K Semba and J. i. Inoue    

Abstract:

Tumour necrosis factor receptor-associated factor (TRAF)-interacting protein with a forkhead-associated domain (TIFA) activates TRAF6 to induce NF-B 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.

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