Perturbations in O-linked beta-N-acetylglucosamine protein modification cause severe defects in mitotic progression and cytokinesis

J Biol Chem. 2005 Sep 23;280(38):32944-56. doi: 10.1074/jbc.M503396200. Epub 2005 Jul 18.


The dynamic modification of nuclear and cytoplasmic proteins with O-linked beta-N-acetylglucosamine (O-GlcNAc) is a regulatory post-translational modification that is rapidly responsive to morphogens, hormones, nutrients, and cellular stress. Here we show that O-GlcNAc is an important regulator of the cell cycle. Increased O-GlcNAc (pharmacologically or genetically) results in growth defects linked to delays in G2/M progression, altered mitotic phosphorylation, and cyclin expression. Overexpression of O-GlcNAcase, the enzyme that removes O-GlcNAc, induces a mitotic exit phenotype accompanied by a delay in mitotic phosphorylation, altered cyclin expression, and pronounced disruption in nuclear organization. Overexpression of the O-GlcNAc transferase, the enzyme that adds O-GlcNAc, results in a polyploid phenotype with faulty cytokinesis. Notably, O-GlcNAc transferase is concentrated at the mitotic spindle and midbody at M phase. These data suggest that dynamic O-GlcNAc processing is a pivotal regulatory component of the cell cycle, controlling cell cycle progression by regulating mitotic phosphorylation, cyclin expression, and cell division.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • 3T3-L1 Cells
  • Acetylglucosamine / chemistry*
  • Adenoviridae / genetics
  • Animals
  • Blotting, Western
  • Cell Cycle
  • Cell Division
  • Cell Nucleus / metabolism
  • Cell Proliferation
  • Cytokinesis
  • Cytoplasm / metabolism
  • Flow Cytometry
  • Glycosylation
  • HeLa Cells
  • Humans
  • Mice
  • Microscopy, Confocal
  • Microscopy, Fluorescence
  • Mitosis*
  • NIH 3T3 Cells
  • Phenotype
  • Phosphorylation
  • Thymidine / chemistry
  • Time Factors


  • Acetylglucosamine
  • Thymidine