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

Rhett A. Kovall*, Brian Gebelein, David Sprinzak, Raphael Kopan

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

Abstract

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.

Original languageEnglish
Pages (from-to)228-241
Number of pages14
JournalDevelopmental Cell
Volume41
Issue number3
DOIs
StatePublished - 8 May 2017

Funding

FundersFunder number
National Science Foundation1715822
National Cancer InstituteR01CA178974

    Keywords

    • Notch signaling
    • mechanism
    • review
    • transcription

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