Fine-Tuning Limited Proteolysis: A Major Role for Regulated Site-Specific O-Glycosylation

Trends Biochem Sci. 2018 Apr;43(4):269-284. doi: 10.1016/j.tibs.2018.02.005. Epub 2018 Mar 2.


Limited proteolytic processing is an essential and ubiquitous post-translational modification (PTM) affecting secreted proteins; failure to regulate the process is often associated with disease. Glycosylation is also a ubiquitous protein PTM and site-specific O-glycosylation in close proximity to sites of proteolysis can regulate and direct the activity of proprotein convertases, a disintegrin and metalloproteinases (ADAMs), and metalloproteinases affecting the activation or inactivation of many classes of proteins, including G-protein-coupled receptors (GPCRs). Here, we summarize the emerging data that suggest O-glycosylation to be a key regulator of limited proteolysis, and highlight the potential for crosstalk between multiple PTMs.

Keywords: G-protein-coupled receptors; GalNAc-Ts; O-glycosylation; PTM; proteases; proteolytic processing.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Disintegrins / metabolism*
  • Glycosylation
  • Humans
  • Metalloproteases / metabolism*
  • Protein Processing, Post-Translational*
  • Proteolysis*


  • Disintegrins
  • Metalloproteases