Apoptosis is induced by certain cytokines including TNF and Fas ligand of the TNF family through their death domain containing receptors, TNF-R1 and Fas. Several novel death receptors including DR3, DR4, DR5, and DR6 were recently identified. Cell death signal is transduced by death domain containing adapter molecules through the interaction with death domain of these death receptors. A novel TNF-R1 interacting protein was recently identified and designated SODD for silencer of death domains. SODD associates with the death domain of TNF-R1 and prevents constitutive activation of TNF-R1 signaling. TNF treatment releases SODD and permits adapter molecules such as TRADD recruiting to the active TNF-R1 complex, which activates TNF signaling pathways. SODD also interacts with DR3. SODD is ubiquitously expressed in human tissues and cell lines.
