Recombining binding protein suppressor of hairless (RBPJ) (RBPJ)

Recombining binding protein suppressor of hairless (RBPJ), also known as CSL, is a highly conserved DNA-binding protein that serves as the central nuclear effector of the Notch signaling pathway (UniProt P23560). In the absence of Notch signaling, RBPJ acts as a transcriptional repressor by binding to specific DNA motifs and recruiting co-repressor complexes to target gene promoters (PubMed: 24510445). Upon activation of the Notch receptor, the Notch intracellular domain (NICD) translocates to the nucleus and binds to RBPJ, displacing the repressors and recruiting co-activators like Mastermind-like (MAML) to initiate the transcription of genes involved in cell fate, proliferation, and survival (PubMed: 21378750). Dysregulation of this RBPJ-mediated transcriptional switch is a key driver in various malignancies, particularly T-cell acute lymphoblastic leukemia and several solid tumors where Notch signaling is constitutively active (PubMed: 29233917). Therapeutic targeting of RBPJ focuses on small molecules or peptides, such as CB-103, that disrupt the assembly of the RBPJ-NICD-MAML ternary complex, providing a more targeted approach to inhibiting Notch-driven oncogenesis compared to broad-spectrum gamma-secretase inhibitors (PubMed: 31515461).

Other names

CSLCBF1RBP-JRBP-JKRBPSUHKBF2IGKJRBSuppressor of hairless homolog

Inhibition of the Notch transcription complex by disrupting the protein-protein interaction between RBPJ, the Notch intracellular domain (NICD), and Mastermind-like (MAML) co-activators.