Cleaved Notch1 (Val1744) (D3B8) Rabbit mAb

Notch proteins (Notch1-4) are a family of transmembrane receptors that play important roles in development and the determination of cell fate (1). 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 (Notch intracellular domain, NICD) (2). 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 (3,4).The NICD of murine Notch1 is released (activated) by cleavage between Gly1743 and Val1744 (corresponding to Gly1753/Val1754 in human Notch1) (3, 4). Mutations that result in constitutive activation of Notch1 are associated with many different cancers, including a majority of cases of T cell acute lymphoblastic leukemia (T-ALL). Activation may be due to mutations in Notch1 itself, or in components of the ubiquitin ligase complex that negatively regulates the Notch signaling pathway (5-6). 1.Artavanis-Tsakonas, S. et al. (1999) Science 284, 770-6. 2.Chan, Y.M. and Jan, Y.N. (1998) Cell 94, 423-6. 3.Schroeter, E.H. et al. (1998) Nature 393, 382-6. 4.Rand, M.D. et al. (2000) Mol Cell Biol 20, 1825-35. 5.Weng, A.P. et al. (2004) Science 306, 269-71. 6.Thompson, B.J. et al. (2007) J Exp Med 204, 1825-35.