biostudies-literatureKovall RANCI NIH HHS228-241https://www.ebi.ac.uk/biostudies/studies/S-EPMC5492985biostudies-literatureUnknown41(3)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.Developmental cellThe Canonical Notch Signaling Pathway: Structural and Biochemical Insights into Shape, Sugar, and Force.PMC5492985R01 CA178974Sprinzak DGebelein BKovall RAKopan RfalseThe Canonical Notch Signaling Pathway: Structural and Biochemical Insights into Shape, Sugar, and Force.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.2017-01-01T00:00:00Z2017 May2024-11-11T19:54:09.538Z2019-03-26T23:35:55ZS-EPMC54929852848612910.1016/j.devcel.2017.04.001