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

Figure 1

Notch receptors and their ligands. Signal-initiating cells express Notch ligands of the Delta-like (DLL1, DDL3, DLL4) or Jagged families (JAG1, JAG2). Common structural features of all ligands are the Epithelial growth factor-like (EGF) repeats and the distal amino-terminal domain called DSL (Delta, Serrate, and Lag-2). DSL is involved in receptor binding. Additionally, JAG1 and JAG2 contain a proximal cysteine-rich (CR) domain between the EGF-like repeats and the plasma membrane. In humans there are four heterodimeric Notch receptors (Notch1-4; N1-N4). The extracellular Notch receptor domain contains EGF-like repeats, a cysteine-rich LIN-12 repeats (LIN domain) that prevents ligand-independent activation, and the proximal heterodimerization domain (HD). The cytoplasmic domain contains an RBP-J-associated molecule (RAM) domain (closest to the cell membrane) followed by ankyrin repeats (ANK) that bind to the CSL (CBF1/RBP-J𝜅/Suppressor of Hairless/LAG-1) transcription factor, a transactivation domain (TAD; only Notch 1 and 2), and a PEST (proline, glutamic acid, serine, threonine) sequence that is important for stabilization of the protein (adapted from [1]).