Background information
MIB1 is a 1006 amino acid E3 ubiquitin ligase that activates the Notch ligand, Delta. MIB1 ubiquinates Delta by binding to its intracellular domain, leading to the endocytosis and eventual degradation of the Delta receptor, which, paradoxically, results in the up-regulation of receptor activity and enhances Notch signaling. MIB1 also interacts with DAPK, a protein that plays an important role in the regulation of apoptosis. Ubiquination of DAPK leads to inhibition of caspase-dependent apoptosis, therefore it is likely that overexpression of MIB1 can lead to tumor growth. Although it seems to be widely expressed at low levels, MIB1 is expressed at highest concentrations in the CNS and ovary. Both DAPK and MIB1 are overexpressed in epileptic brain tissue, suggesting that they probably cooperate as regulators of neuronal death in epilepsy.
