MADD is Highly Homologous to a Rab3 Guanine-Nucleotide Exchange Protein (Rab3-GEP)

The MADD protein (death domain MAP kinase activator) has recently been identified as a death-domain-containing protein involved in the activation of mitogen-activated protein (MAP) kinase and arachadonic acid release mediated by the tumor necrosis factor receptor type 1 (TNFR1). The death domain of MADD (amino acids 1281–1356) can bind to the death domain of TNFR1 and can activate MAP kinases. Overexpression of MADD has no effect on the induction of apoptosis, however. Thus, although the presence of a death domain is suggestive of a potential protein–protein interaction, it does not always implicate a protein in the apoptotic process.