When NICD binds to RBPJ, the co-repressor (e.g., CSL) dissociates, and the co-activator, MAML, binds and activates gene transcription.451,452 The precise regulation of Notch signaling is essential for tissue development and cellular function, and dysregulation of this pathway contributes to a variety of diseases, particularly cancer and developmental disorders.453–456 Abnormal activation of Notch signaling can lead to cancer, and conversely, inhibition can lead to developmental disorders. This evidence concerns the gene RBPJ and cancer.