Title:The Molecular Basis of Notch Signaling Regulation: A Complex Simplicity
Volume: 14
Issue: 1
Author(s): R. Palermo, S. Checquolo, D. Bellavia, C. Talora and I. Screpanti
Affiliation:
Keywords:
Acetylation, canonical, ligands, non-canonical, notch, phosphorylation, processing, transcriptional
activity, ubiquitination.
Abstract: The Notch receptors have attracted considerable attention for their ability to control cellular functions
that regulate embryo development and tissue homeostasis. Notch receptors act by controlling the expression
of a specific set of target genes. If Notch signaling system can be so simple, and yet so complex in its
pleiotropic effects, then a sophisticated network of regulatory mechanisms is required to maintain the control
over the initiation, activity and termination of this signaling pathway. A multitude of regulatory mechanisms has
been discovered that controls the interaction of Notch receptors with their ligands, the assembling of a Notch
transcriptional activation complex and the termination of Notch signals. The intracellular and extracellular
domains of the Notch receptors are synthesized as single proteins, pairing with each other during their
trafficking through the exocytotic route. The mechanisms operating in the phase preceding the generation of
the heterodimeric signal-competent Notch receptors can be as elaborate and physiologically important as
those operating downstream of Notch receptor activation. These regulatory mechanisms, which are essential
to understand the role of Notch signaling in human physiology and pathology are reviewed here.
