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

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


  • Tsitsikov EN
  • Laouini D
  • Dunn IF
  • Sannikova TY
  • Davidson L
  • Alt FW
  • Geha RS



Publication Data

October 23, 2001

Associated Grants

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

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