O-GlcNAcylation Antagonizes Phosphorylation of CDH1 (CDC20 Homologue 1)

J Biol Chem. 2016 Jun 3;291(23):12136-44. doi: 10.1074/jbc.M116.717850. Epub 2016 Apr 14.

Abstract

The anaphase promoting complex/cyclosome (APC/C) orchestrates various aspects of the eukaryotic cell cycle. One of its co-activators, Cdh1, is subject to myriad post-translational modifications, such as phosphorylation and ubiquitination. Herein we identify the O-linked N-acetylglucosamine (O-GlcNAc) modification that occurs on Cdh1. Cdh1 is O-GlcNAcylated in cultured cells and mouse brain extracts. Mass spectrometry identifies an O-GlcNAcylated peptide that neighbors a known phosphorylation site. Cell synchronization and mutation studies reveal that O-GlcNAcylation of Cdh1 may antagonize its phosphorylation. Our results thus reveal a pivotal role of O-GlcNAcylation in regulating APC/C activity.

Keywords: Cdh1; O-linked N-acetylglucosamine (O-GlcNAc); O-linked N-acetylglucosamine (O-GlcNAc) transferase (OGT); anaphase promoting complex/cyclosome (APC/C); cell cycle; mitosis; phosphorylation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylglucosamine / metabolism*
  • Acylation
  • Anaphase-Promoting Complex-Cyclosome / genetics
  • Anaphase-Promoting Complex-Cyclosome / metabolism*
  • Animals
  • Binding Sites / genetics
  • Cdh1 Proteins / genetics
  • Cdh1 Proteins / metabolism*
  • Glycosylation
  • HeLa Cells
  • Humans
  • Immunoblotting
  • Mice
  • Mutation
  • N-Acetylglucosaminyltransferases / genetics
  • N-Acetylglucosaminyltransferases / metabolism
  • Phosphorylation
  • Protein Binding
  • Protein Processing, Post-Translational*
  • Tandem Mass Spectrometry

Substances

  • Cdh1 Proteins
  • Anaphase-Promoting Complex-Cyclosome
  • N-Acetylglucosaminyltransferases
  • Acetylglucosamine