Notch, metabolism and macrophages

Notch signaling is a highly conserved and critical pathway that integrates environmental cues to specify cell fate during development. Notch is a single transmembrane receptor with 4 isoforms (Notch1 to 4) and five known Notch ligands. Notch activation is initiated by ligand binding, which leads to sequential proteolytic cleavage and liberation of Notch intracellular domain (NICD) from the membrane. The NICD translocates into the nucleus where it interacts with a DNA binding protein CSL and other nuclear proteins to form a transcriptional co-activator complex [1]. Recent studies have shown that Notch pathway is also involved in liver regeneration/repair, carcinogenesis, metabolism, and modulation of inflammatory response by regulating macrophage polarization through toll-like receptor 4 and/or NF-κB pathway [2]. It is now clear that Notch functions in cell fate determination extend beyond development.