Recognizes endogenous levels of NOTCH3 protein.
Notch proteins (Notch1-4) 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 comprised of a large extracellular ligand-binding domain, a single-pass transmembrane domain, and a smaller cytoplasmic subunit (Notch intracellular domain, NICD). Binding of Notch receptors to ligands of the Delta-Serrate-Lag2 (DSL) 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 the Notch family and is processed similar to Notch1 It is expressed primarily in arterial smooth muscle cells (SMC). Mutations altering the number of cysteine residues in the Notch3 extracellular region are associated with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), a hereditary angiopathy leading to strokes and dementia in adults. Recent studies indicate that Notch3 is overexpressed in many types of cancer.
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