MAP kinase-activating death domain protein (MADD) regulates cell proliferation, survival and death through alternative mRNA splicing. Different isoforms have different effects: isoform 5 increases cell proliferation whereas isoform 2 decreases it; isoform 1 is susceptible to inducing apoptosis, isoform 5 is resistant []. MADD activates RAB3A, RAB3C and RAB3D by converting them from GDP-bound inactive forms to GTP-bound active forms []. MADD is a component of the TNFRSF1A signaling complex, linking the type 1 tumor necrosis factor receptor TNFRSF1A with MAP kinase activation []. MADD contains a tripartite DENN domain. In the nematode Caenorhabditis elegans, MADD is also known as regulator of presynaptic activity aex-3 [].
