NOTCH1 and cancer: 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.