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Sci. STKE, 23 November 2004
Vol. 2004, Issue 260, p. tw418
[DOI: 10.1126/stke.2602004tw418]

EDITORS' CHOICE

IMMUNOLOGY TRAF2, Master Regulator of NF-{kappa}B

TRAF2 is an adaptor protein and ubiquitin ligase that is involved in mediating signals from the tumor necrosis factor receptors (TNFRs). Grech et al. investigated B cell signaling and proliferation in TRAF2-deficient mice. TRAF2-deficient B cells accumulated in conditionally deficient mice, leading to enlarged spleen and lymph nodes. Analysis of the TRAF2-deficient B cells showed that the processing of NF-{kappa}B2 p100 precursor into the cleaved p52 subunit was increased along with an increase in the DNA-binding activity of the p52 and RelB subunits, which indicates constitutive activation of the noncanonical NF-{kappa}B pathway. In addition, the cells were defective in activation of the canonical NF-{kappa}B pathway by antibodies that activate the TNFR family member, CD40, and did not show stimulation of proliferation, an increase in RelA activation, or phosphorylation and degradation of I{kappa}Bα, the inhibitor of NF-{kappa}B, that occurs in wild-type cells. Processing of the NF-{kappa}B precursor was not further stimulated by BAFF, a ligand for another member of the TNFR family that signals through the noncanonical pathway, or antibodies to CD40, suggesting that in the absence of TRAF2, processing of NF-{kappa}B is already maximal. BAFF and the noncanonical NF-{kappa}B pathway are involved in B cell maturation, and this pathway appears to be negatively regulated by TRAF2. In contrast, B cell activation through CD40 signaling to the canonical NF-{kappa}B pathway requires TRAF2 and is stimulated by TRAF2-mediated signaling. Thus, TRAF2 acts as a dual functional regulator of the NF-{kappa}B pathways.

A. R. Grech, M. Amesbury, T. Chan, S. Gardam, A. Basten, R. Brink, TRAF2 differentially regulates the canonical and noncanonical pathways of NF-{kappa}B activation in mature B cells. Immunity 21, 629-642 (2004). [Online Journal]

Citation: TRAF2, Master Regulator of NF-{kappa}B. Sci. STKE 2004, tw418 (2004).



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