Glycosylation regulates Notch signalling

  title={Glycosylation regulates Notch signalling},
  author={Nicola Haines and Kenneth D. Irvine},
  journal={Nature Reviews Molecular Cell Biology},
Intracellular post-translational modifications such as phosphorylation and ubiquitylation have been well studied for their roles in regulating diverse signalling pathways, but we are only just beginning to understand how differential glycosylation is used to regulate intercellular signalling. Recent studies make clear that extracellular post-translational modifications, in the form of glycosylation, are essential for the Notch signalling pathway, and that differences in the extent of… 

Role of glycosylation of Notch in development.

Glycosylated Notch and Cancer

The importance and recent updates on the role of glycosylated Notch proteins in tumorigenesis and tumor metastasis are summarized.

Notch signalling: a simple pathway becomes complex

  • S. Bray
  • Biology
    Nature Reviews Molecular Cell Biology
  • 2006
Although the intracellular transduction of the Notch signal is remarkably simple, with no secondary messengers, this pathway functions in an enormous diversity of developmental processes and its dysfunction is implicated in many cancers.

The role of Adams in Notch signaling.

The role of ectodomain shedding is reviewed in RIP of the NOTCH signaling pathway, a highly conserved cell-cell communication pathway that mediates cell fate decisions during development and in adult tissues.

Notch signaling: the core pathway and its posttranslational regulation.

Glycosylation in Cellular Mechanisms of Health and Disease

Regulation of Notch signaling by glycosylation.

  • P. Stanley
  • Biology
    Current opinion in structural biology
  • 2007

A Notch updated

The study of the modulation of the pathway in different cellular contexts has revealed many layers of regulation, including complex sugar modifications in the extracellular domain as well as transit of Notch through defined cellular compartments, including specific endosomes.

Multifaceted regulation of Notch signaling by glycosylation.

A detailed discussion on how various steps during Notch activation are regulated by glycans is provided, which will potentially be of benefit to investigators examining the contribution of glycosylation to other developmental processes.

Role of glycans and glycosyltransferases in the regulation of Notch signaling.

Studying how sugar modification modulates Notch signaling provides a framework for better understanding the role of glycosylation in animal development and might offer new tools to manipulate NotCh signaling for therapeutic purposes.



Regulation of signal transduction pathways in development by glycosylation.

UDP–sugar transporter implicated in glycosylation and processing of Notch

The results suggest that changes in nucleotide–sugar levels can differently affect Wingless and two distinct aspects of Notch signalling.

Dual role of the fringe connection gene in both heparan sulphate and fringe-dependent signalling events

A new gene is described, fringe connection (frc), that encodes a nucleotide–sugar transporter that transfers UDP–glucuronic acid, UDP–N-acetylglucosamine and possibly UDP–xylose from the cytoplasm into the lumen of the endoplasmic reticulum/Golgi.

Notch signalling in Drosophila: three ways to use a pathway.

  • S. Bray
  • Biology
    Seminars in cell & developmental biology
  • 1998
These illustrations illustrate how the activity of the Notch signalling pathway can be modulated both at the cell surface, through availability and effectiveness of ligand interactions, and inside the cell, through effects on the transduction pathway and the responsiveness of target genes.

Fringe is a glycosyltransferase that modifies Notch

The post-translational modification of Notch by Fringe represents a striking example of modulation of a signalling event by differential receptor glycosylation and identifies a mechanism that is likely to be relevant to other signalling pathways.

Modulators of Notch signaling.

Genetic studies indicate that distinct modulators are deployed during distinct modes of Notch signaling, which presumably influence signal transduction steps after receptor activation.

Variations on the Notch pathway in neural development

Protein O-fucosyltransferase 1 is an essential component of Notch signaling pathways

  • S. ShiP. Stanley
  • Biology
    Proceedings of the National Academy of Sciences of the United States of America
  • 2003
It is shown that mouse embryos lacking protein O-fucosyltransferase 1 die at midgestation with severe defects in somitogenesis, vasculogenesis, cardiogenesis, and neurogenesis, and the phenotype is similar to that of embryos lacking downstream effectors of all Notch signaling pathways such as presenilins or RBP-Jκ.