First Author | Tsitsikov EN | Year | 2001 |
Journal | Immunity | Volume | 15 |
Issue | 4 | Pages | 647-57 |
PubMed ID | 11672546 | Mgi Jnum | J:72327 |
Mgi Id | MGI:2152473 | Doi | 10.1016/s1074-7613(01)00207-2 |
Citation | Tsitsikov EN, et al. (2001) Traf1 is a negative regulator of tnf signaling. enhanced tnf signaling in traf1-deficient mice. Immunity 15(4):647-57 |
abstractText | 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-kappaB 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. |