Disease relevance of Traf1

• TNF receptor-associated factor (TRAF) 6 is a key signaling adaptor for RANK, and its deficiency leads to similar osteopetrosis [1].
• TNF receptor-associated factor (TRAF) domain and Bcl-2 cooperate to induce small B cell lymphoma/chronic lymphocytic leukemia in transgenic mice [2].
• Transgenic mice overexpressing in B lymphocytes either Bcl-2 or a TNF receptor-associated factor (TRAF)2 mutant lacking the N-terminal RING and zinc finger domains located at the N terminus of the molecule (TRAF2DN), which mimics TRAF1, developed lymphadenopathy and splenomegaly due to polyclonal B cell expansion [2].
• Foamy macrophages within lung granulomas of mice infected with Mycobacterium tuberculosis express molecules characteristic of dendritic cells and antiapoptotic markers of the TNF receptor-associated factor family [3].
• Multiple carboxyl-terminal regions of the EBV oncoprotein, latent membrane protein 1, cooperatively regulate signaling to B lymphocytes via TNF receptor-associated factor (TRAF)-dependent and TRAF-independent mechanisms [4].

High impact information on Traf1

• TNF receptor-associated factor (TRAF) proteins are candidate signal transducers that associate with the cytoplasmic domains of members of the tumor necrosis factor (TNF) receptor superfamily [5].
• 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 [6].
• 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 [6].
• TRAF1(-/-) mice are viable and have normal lymphocyte development [6].
• The Traf-linked tumor necrosis factor receptor family member CD27 is known as a T cell costimulatory molecule [7].

Biological context of Traf1

• For each of these receptors, multiple mechanisms of TRAF regulation contribute to signal transduction and the ultimate effect on the B cell [8].
• Restriction mapping and Southern blotting analysis revealed that the TRAF1 gene comprises 10 exons and 9 intervening introns and spreads over 18 kb of genomic DNA [9].
• 5'-RACE analysis of the TRAF1 transcript using mRNA from activated spleen B cells revealed several transcription start sites between positions -42 to +4 relative to the 5'end of the murine TRAF1 cDNA sequence [9].

Anatomical context of Traf1

• TNF Receptor-Associated Factor 2-Dependent Canonical Pathway Is Crucial for the Development of Peyer's Patches [10].

Associations of Traf1 with chemical compounds

• In addition we show that TRAF1 mRNA is not expressed in non-stimulated lymphocytes but can be induced upon activation with different stimuli, including anti-CD3, anti-IgM, anti-CD40 antibodies, LPS, or a combination of phorbol-12-myristate-13-acetate and ionomycin [9].

Other interactions of Traf1

• Despite relatively mild lung injury, intratracheal TNF-alpha-treated TRAF1-/- mice exhibited marked liver injury with an approximate fivefold increase in serum liver enzyme levels as compared to wild-type mice [11].

Analytical, diagnostic and therapeutic context of Traf1

• Cells isolated by bronchoalveolar lavage from intratracheally treated TRAF1-/- mice produced more TNF-alpha than cells from treated wild-type mice, suggesting that lung cells contributed to elevated serum TNF-alpha [11].
• This is the first in situ hybridization analysis of expression of a tumor necrosis factor (TNF) receptor associated factor (TRAF) during development [12].

References