Protein degradation: Four E3s for the Notch pathway

The Notch pathway is a conserved signal transduction cascade which is essential for pattern formation and the proper execution of a wide array of cell-fate decisions. As only modest differences in Notch pathway activity suffice to determine dramatic differences in cellular behavior, this pathway is tightly regulated by a variety of molecular mechanisms. Several recent studies now highlight the importance of the ubiquitination pathway in the control of Notch pathway activity. This review will summarize recent advances in understanding the function of four E3 ubiquitin ligases that regulate levels of the Notch receptor and other components of this pathway. These include Suppressor of deltex/Itch and Sel-10, which both regulate Notch, Neuralized, which regulates the Notch ligand Delta, and LNX, which regulates the Notch antagonist Numb.