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TRAF1 is a negative regulator of TNF signaling. enhanced TNF signaling in TRAF1-deficient mice.

Immunity | Oct 23, 2001

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.

Pubmed ID: 11672546 RIS Download

Mesh terms: Animals | Antibodies, Monoclonal | Antigens, CD3 | Apoptosis | B-Lymphocytes | Cells, Cultured | Immunoglobulins | Kinetics | Lymphocyte Activation | Mice | Mice, Knockout | Necrosis | Proteins | Signal Transduction | Skin Diseases | Superantigens | T-Lymphocytes | TNF Receptor-Associated Factor 1 | Tumor Necrosis Factor-alpha

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Associated grants

  • Agency: NIAID NIH HHS, Id: AI-35714
  • Agency: NIAID NIH HHS, Id: AI-42031

Mouse Genome Informatics (Data, Gene Annotation)

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