Future Perspectives: Therapeutic Targeting of Notch Signalling May Become a Strategy in Patients Receiving Stem Cell Transplantation for Hematologic Malignancies

Figure 2

Notch canonical signalling pathway. The figure shows an overview of the canonical Notch signalling pathway (adapted from [8]). The signalling is initiated by ligand binding to Notch receptor (1). This binding initiates two subsequent proteolytic cleavages of the Notch receptor by the ADAM family protease (2) and the γ-secretase, respectively (3). The Notch IntraCellular Domain (NICD) is thereby released to the cytoplasm (4) and translocates to the nucleus where NICD heterodimerizes with the DNA-binding transcription factor CBF1 (also named CSL or Rbp-j). Additional coactivators are also recruited, including mastermind-like proteins (MAML1-3) ultimately leading to induction of transcriptional expression of downstream target genes, including those belonging to the Hes and Hey families.