IMMUNOLOGY TRAF1 Is a Negative Regulator

Abstract: Most of the tumor necrosis factor- (TNF-) receptor-associated factor (TRAF) family of proteins are characterized by having RING finger domains, several Zn²⁺ fingers, and a COOH-terminal TRAF domain. TRAF1 is unusual because it contains only one Zn²⁺ finger, and no RING fingers, in addition to the TRAF domain. Until now, the function of TRAF1 in TNFR signaling has been unclear. Tsitsikov et al. created TRAF1-deficient mice and observed that T and B cell development and B cell proliferation were normal, but that T cell receptor (TCR)-mediated T cell proliferation was increased. Enhanced proliferation of traf1^-/- T cells in response to TCR signals was ameliorated by treating the cells with a TNFR2-blocking antibody, suggesting that TRAF1 acts to negatively regulate signaling through TNFR2. Additionally, TNF--dependent signaling in TRAF1-deficient T cells resulted in increased activation of NF-B and AP-1. Thus, TRAF1 might function by competing with other TRAF proteins for binding sites on TNFR2, or by sequestering other TRAF family proteins and preventing their binding to TNFR2.

E. N. Tsitsikov, D. Laouini, I. F. Dunn, T. Y. Sannikova, L. Davidson, F. W. Alt, R. S. Geha, TRAF1 is a negative regulator of TNF signaling: Enhanced TNF signaling in TRAF1-deficient mice. Immunity 15, 647-657 (2001). [Online Journal]