Figure 3. The Notch signalling pathway and dMyc-mediated cell growth.

(A) The Notch receptor is processed sequentially by three enzymatic activities. In the Golgi compartment, Notch is cleaved by furin to produce two covalently linked fragments, which form the mature protein. After reaching the cell surface, Notch is activated and processed following the interaction with a ligand and an ADAM protease to release its ectodomain into the extracellular matrix. This shedding event renders the truncated membrane-bound Notch remnant accessible to the action of the γ-secretase complex, which cuts Notch within the confines of the lipid bilayer to release the Notch intracellular domain, NICD. This gene regulatory fragment then moves to the nucleus where it interacts with various co-activators, including CSL and MAM to regulate target gene expression. (B) The growth regulator dMyc is a target of the Notch pathway. One of the targets regulated by dMyc is the translation initiation factor eIF4E, which acts as a cell growth mediator. The dMyc/eIF4E regulatory loop functions to control cell growth and cell fate choices in type II neuroblast lineages (based on [100]).