Notch proteins are a family of transmembrane receptors that play important roles in development and the determination of cell fate. Mature Notch receptors are processed and assembled as heterodimeric proteins, with each dimer composed of a large extracellular ligand-binding domain, a single-pass transmembrane domain, and a smaller cytoplasmic subunit. Binding of Notch receptors to ligands of the Delta-Serrate-Lag2 family triggers heterodimer dissociation, exposing the receptors to proteolytic cleavages; these result in release of the NICD, which translocates to the nucleus and activates transcription of downstream target genes.Notch3 is a member of notch family and processed similar to notch1. It is expressed primarily in arterial smooth muscle cells. Mutations altering the number of cysteine residues in the notch3 extracellular region are associated with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy, a hereditary angiopathy leading to strokes and dementia in adults. Recent studies indicates that notch3 is overexpressed in many types of cancers.
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