Upregulation of NF-κB-Dependent Gene Expression Mediated by the p75 Tumor Necrosis Factor Receptor

Tumor necrosis factor (TNF-α) interacts with two transmembrane receptor proteins, p55^TNFR and p75^TNFR, which are members of a family of cell surface molecules that include the Fas antigen, CD27, CD30, CD40, OX40, a Shope fibroma viral protein, and the low-affinity p75 neurotrophin receptor. Although the p55 TNF receptor has been shown to be primarily responsible for the biologic responses of TNF-α, the exact involvement of the p75 TNF receptor in signaling events is unclear. Here we show that expression of a human cDNA clone for p75 in COS-1 and 3T3 cells results in the constitutive activation of an TNF-inducible NF-κB-containing promoter. Analysis of a number of chimeric p75 receptor cDNA constructs further suggests that this activity requires the cytoplasmic domain of the p75 receptor. These results therefore indicate that the p75 TNF receptor is capable of mediating signal transduction.