The Canonical Notch Signaling Pathway: Structural and Biochemical Insights into Shape, Sugar, and Force

Publication date: 8 May 2017
Source:Developmental Cell, Volume 41, Issue 3
Author(s): Rhett A. Kovall, Brian Gebelein, David Sprinzak, Raphael Kopan
The Notch signaling pathway relies on a proteolytic cascade to release its transcriptionally active intracellular domain, on force to unfold a protective domain and permit proteolysis, on extracellular domain glycosylation to tune the forces exerted by endocytosed ligands, and on a motley crew of nuclear proteins, chromatin modifiers, ubiquitin ligases, and a few kinases to regulate activity and half-life. Herein we provide a review of recent molecular insights into how Notch signals are triggered and how cell shape affects these events, and we use the new insights to illuminate a few perplexing observations.

Teaser

In this review, Kovall et al. describe structure-based insights into Notch receptor/ligand interactions, the proteins involved in receptor modifications and cleavage, details on what forces are required to activate Notch, how cell shape might affect this process, and how the active NICD molecule mediates changes in gene expression.


http://ift.tt/2q0Igaq