SODD peptide

Several cell surface receptors that are involved in apoptosis contain intracellular death domains and are capable of triggering apoptosis when activated by their respective ligands. Due to presence of these death domains and presence of various stimuli in the serum as well as overexpression leading to receptor oligomerization, which leads to constitutive activation of the apoptotic pathway, it has been extremely difficult to generate permanent cell lines overexpressing specific receptors in culture. However, in normal states, this death domain activity is silenced presumably due to presence of other cellular factors. Recently, a DR3 associated protein has been isolated by yeast two-hybrid interaction assays. This cDNA encoding a 457-amino acid protein has been named as SODD (Silencer of Death Domain). SODD also associates with the intracellular domains of TNF-R1, but not with those of TNF-R2, Fas, DR4, or DR5. SODD overexpression suppressed the TNF induced cell death as well as NF-kB activation. SODD may act as a negative regulatory protein that is normally associated with death domain of TNF-R1 and probably inhibit self-oligomerization properties of death domain and maintain TNF-R1 in an inactive, monomeric state.