Significance of glycosylation in Notch signaling

Biochem Biophys Res Commun. 2014 Oct 17;453(2):235-42. doi: 10.1016/j.bbrc.2014.05.115. Epub 2014 Jun 6.

Abstract

Notch signaling is essential for cell-fate specification in metazoans, and dysregulation of the pathway leads to a variety of human diseases including heart and vascular defects as well as cancer. Glycosylation of the Notch extracellular domain has emerged as an elegant means for regulating Notch activity, especially since the discovery that Fringe is a glycosyltransferase that modifies O-fucose in 2000. Since then, several other O-glycans on the extracellular domain have been demonstrated to modulate Notch activity. Here we will describe recent results on the molecular mechanisms by which Fringe modulates Notch activity, summarize recent work on how O-glucose, O-GlcNAc, and O-GalNAc glycans affect Notch, and discuss several human genetic disorders resulting from defects in Notch glycosylation.

Keywords: EGF repeat; Notch signaling; O-Glycosylation.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Animals
  • Congenital Disorders of Glycosylation / genetics
  • Congenital Disorders of Glycosylation / metabolism
  • Fucose / chemistry
  • Glucose / chemistry
  • Glycosylation
  • Glycosyltransferases / metabolism
  • Humans
  • Models, Molecular
  • Polysaccharides / chemistry
  • Polysaccharides / metabolism
  • Protein Interaction Domains and Motifs
  • Protein Processing, Post-Translational
  • Receptors, Notch / chemistry
  • Receptors, Notch / genetics
  • Receptors, Notch / metabolism*
  • Repetitive Sequences, Amino Acid
  • Signal Transduction

Substances

  • Polysaccharides
  • Receptors, Notch
  • Fucose
  • Glycosyltransferases
  • Glucose