Targeting the Notch receptor dimerization domain to inhibit Notch signalling—A new avenue of therapeutics

Notch signalling is an evolutionarily conserved signalling pathway that directs cell growth and differentiation across multiple tissue types, and its regulation must be controlled across the lifespan. Aberrant Notch signalling due to genetic mutations that occur within the negative regulatory region of the Notch 1 gene is linked to the development of acute T-cell leukaemia in humans. This discovery has led to a concerted effort to understand how Notch receptor signalling is regulated in mammalian cells. Liu et al. have developed a range of novel peptide inhibitors that target the heterodimerization domain within the negative regulatory region of the Notch receptor. They show that the peptide inhibitors are specific to a Notch receptor paralogue. The possible biological and therapeutic consequences are discussed.