Purified anti-Notch 1

Notch1, also known as neurogenic locus notch homolog protein 1, is a large >270 kD protein that functions as a receptor for the membrane ligands Jagged1, Jagged2 and Delta1 to regulate cell fate decisions. Upon ligand activation, the transmembrane Notch1 receptor is cleaved by TNF-alpha converting enzyme (TACE) to produce a membrane-associated intermediate fragment (NEXT). This fragment is further cleaved by presenilin-dependent gamma secretase to release a notch-derived peptide containing the intracellular fragment from the membrane. The released Notch intracellular fragment (NICD) translocates to the nucleus and forms a transcriptional complex with the RBP-J kappa transcriptional activator complex to alter differentiation, proliferation, and apoptotic programs. Notch 1 is highly expressed in the brain, lung, and thymus (CD4-CD8- cells and CD4-CD8+ cells) with lower levels of expression observed in the spleen, bone marrow, spinal cord, eyes, mammary gland, liver, intestine, kidney and heart. The transmembrane Notch protein is a heterodimeric protein consisting of a C-terminal fragment and N-terminal fragment (probably linked by disulphide bonds) containing 5 ankyrin repeats, 36 EGF repeats, and 3 Notch/Lin repeats. Notch1 can be modified by phosphorylation. The mN1A monoclonal antibody reacts with the intracellular domain of mouse and human Notch1 and has been reported to have highest affinity for activated intracellular Notch1 and lower affinity for full-length unprocessed/heterodimeric Notch1 forms. This antibody does not recognize rat Notch1 or cross-react with Notch2, 3, or 4.