Neurogenic locus notch homolog protein 3 transcriptional ternary complex (Notch3-RBPJ-MAML)

The Neurogenic locus notch homolog protein 3 (Notch3) transcriptional ternary complex is a nuclear assembly that serves as the primary effector of the canonical Notch3 signaling pathway [1]. This complex is composed of the Notch3 intracellular domain (NICD3), the DNA-binding protein Recombination signal binding protein for immunoglobulin kappa J region (RBPJ, also known as CSL), and a co-activator from the Mastermind-like (MAML) family [2]. Upon ligand-induced activation and subsequent proteolytic cleavage of the Notch3 receptor, NICD3 translocates to the nucleus to form this complex, which displaces transcriptional repressors and recruits histone acetyltransferases to activate target genes like HES1 and HEY1 [1, 2]. Biologically, this complex is vital for vascular smooth muscle cell differentiation and the maintenance of arterial structural integrity [3]. Pathologically, mutations in the Notch3 gene lead to CADASIL, a hereditary small vessel disease, while overactivation of the complex is observed in various cancers, including T-cell acute lymphoblastic leukemia and solid tumors [3, 4]. Pharmacological targeting of this complex involves gamma-secretase inhibitors to prevent NICD3 release, monoclonal antibodies to block receptor activation, or small molecules designed to disrupt the protein-protein interactions within the nuclear complex [5].

Other names

Notch3/RBPJ/MAML complexNICD3/CSL/MAML complexNotch3 signaling complexNotch3 transcriptional activation complex

Inhibition of gamma-secretase-mediated cleavage, blockade of ligand-receptor interaction, and disruption of nuclear transcriptional complex assembly.