Tsitsikov, E. N. et al. TRAF1 is a negative regulator of TNF signaling: enhanced TNF signaling in TRAF1-deficient mice. Immunity 15, 647-657

Division of Immunology, Children's Hospital, Harvard Medical School, Boston, MA 02115, USA.
Immunity (Impact Factor: 21.56). 11/2001; 15(4):647-57. DOI: 10.1016/S1074-7613(01)00207-2
Source: PubMed


TNF receptor-associated factor 1 (TRAF1) is a unique TRAF protein because it lacks a RING finger domain and is predominantly expressed in activated lymphocytes. To elucidate the function of TRAF1, we generated TRAF1-deficient mice. TRAF1(-/-) mice are viable and have normal lymphocyte development. TRAF1(-/-) T cells exhibit stronger than wild-type (WT) T cell proliferation to anti-CD3 mAb, which persisted in the presence of IL-2 or anti-CD28 antibodies. Activated TRAF1(-/-) T cells, but not TRAF1(+/+) T cells, responded to TNF by proliferation and activation of the NF-kappa B and AP-1 signaling pathways. This TNF effect was mediated by TNFR2 (p75) but not by TNFR1 (p55). Furthermore, skin from TRAF1(-/-) mice was hypersensitive to TNF-induced necrosis. These findings suggest that TRAF1 is a negative regulator of TNF signaling.

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    • "This study aimed to confirm whether five SNP markers, found in previous studies to predict responses to anti-TNF treatment of RA patients, are also associated with responses to therapy in a genetic homogeneous Greek population. Additionally, two genes that have previously been shown to correlate with RA development, namely STAT4 rs7574865 and TRAF1/C5 rs1081848 [16–18] were selected for investigation as putative markers of anti-TNF response due to the role of these genes in TNF signaling [19,20]. "
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    • "Activation of the death domains (DD) like TRADD (TNF receptor activated DD) and FADD (Fas ligand activated DD) also activates death pathways, like the caspase-8/caspase- 3/apoptosis pathway, and it likely there is interaction between TRADD and FADD. Not shown in this diagram, TRAF1 is also known to cleave caspase-8 and therefore act in a pro-apoptotic role (Adapted from Tsitikov et al., 2001) [18]. provide the transformed cells. "
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