Recombination signal binding protein for immunoglobulin kappa J region (RBPJ) (RBPJ)

Recombination signal binding protein for immunoglobulin kappa J region (RBPJ), also known as CSL, is the central DNA-binding transcription factor of the Notch signaling pathway [1, 7]. It functions as a molecular switch that dictates cell fate by recruiting either co-repressors to silence genes in the absence of signaling or the Notch intracellular domain (NICD) and co-activators like Mastermind to initiate transcription upon pathway activation [4, 6, 8]. This mechanism is critical for embryonic development, tissue homeostasis, and the maintenance of stem cell populations [1, 14]. Dysregulation of RBPJ is implicated in various pathologies, including Notch-driven cancers such as T-cell acute lymphoblastic leukemia and breast cancer, as well as developmental disorders like Adams-Oliver syndrome [1, 3, 5, 13]. While upstream Notch inhibitors like gamma-secretase inhibitors often suffer from severe gastrointestinal toxicity, directly targeting the RBPJ-dependent transcriptional complex with small molecules or peptides offers a potentially more specific therapeutic approach [2, 5]. Clinical-stage inhibitors like CB-103 and experimental molecules like RIN1 aim to disrupt the assembly of the RBPJ-NICD complex to treat malignancies characterized by aberrant Notch activity [2, 7, 9].

Other names

RBP-JκCBF1CSLRBPSUHIGKJRBTranscription factor RBP-JCentromere-binding factor 1Suppressor of Hairless homolog

Inhibition of the Notch transcription complex by disrupting the assembly of the RBPJ-NICD-MAML1 transcriptional complex