Notch proteins are highly conserved transmembrane receptors that are involved in cell fate regulation in invertebrates 1. While Notch receptors are initially synthesized as single polypeptide chains proteolytic processing results in the formation of a heterodimeric receptor in which the extracellular domain is noncovalently attached to the transmembrane and intracellular (IC) part. The Notch-IC is responsible for signaling and contains a series of ankyrin repeats similar to those found in nuclear factor (NF)-κB. The ligand-dependent release of Notch-IC requires processing by the membrane-associated presenilin which in a mutant form is responsible for familial Alzheimer's disease. The biochemical pathway of Notch-IC dissociation from the receptor is not completely understood but requires at some stage proteolytic cleavage (Fig. 1).
The Notch receptor ligands include Delta, a transmembrane protein that affects adjacent cells expressing Notch receptors 2, but...
