O-GlcNAc a sensor of cellular state: The role of nucleocytoplasmic glycosylation in modulating cellular function in response to nutrition and stress

Natasha E Zachara, Gerald Warren Hart

Research output: Contribution to journalArticle

Abstract

Myriad nuclear and cytoplasmic proteins in metazoans are modified on Ser and Thr residues by the monosaccharide O-linked β-N-acetylglucosamine (O-GlcNAc). The rapid and dynamic change in O-GlcNAc levels in response to extracellular stimuli, morphogens, the cell cycle and development suggests a key role for O-GlcNAc in signal transduction pathways. Modulation of O-GlcNAc levels has profound effects on the functioning of cells, in part mediated through a complex interplay between O-GlcNAc and O-phosphate. In many well-studied proteins, the O-GlcNAc modification and phosphorylation are reciprocal. That is, they occur on different subsets of the protein population, as the site of attachment occurs on the same or adjacent Ser/Thr residues. Recently, O-GlcNAc has been implicated in the etiology of type II diabetes, the regulation of stress response pathways, and in the regulation of the proteasome.

Original languageEnglish (US)
Pages (from-to)13-28
Number of pages16
JournalBiochimica et Biophysica Acta - General Subjects
Volume1673
Issue number1-2
DOIs
StatePublished - Jul 6 2004

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Glycosylation
Nutrition
Acetylglucosamine
Monosaccharides
Sensors
Proteasome Endopeptidase Complex
Nuclear Proteins
Type 2 Diabetes Mellitus
Signal Transduction
Signal transduction
Cell Cycle
Phosphorylation
Proteins
Phosphates
Medical problems
Cells
Modulation
Population

Keywords

  • BAG
  • benzyl-α-GalNAc
  • C-terminal domain
  • casein kinase II
  • CK II
  • CTD
  • endothelial nitric oxide synthase
  • eNOS
  • ER
  • ERK
  • estrogen receptor
  • Heat shock
  • Hyperglycemia
  • N-acetylglucosamine
  • O-GlcNAc
  • Phosphorylation
  • Post-translational modification
  • Stress

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Molecular Biology

Cite this

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title = "O-GlcNAc a sensor of cellular state: The role of nucleocytoplasmic glycosylation in modulating cellular function in response to nutrition and stress",
abstract = "Myriad nuclear and cytoplasmic proteins in metazoans are modified on Ser and Thr residues by the monosaccharide O-linked β-N-acetylglucosamine (O-GlcNAc). The rapid and dynamic change in O-GlcNAc levels in response to extracellular stimuli, morphogens, the cell cycle and development suggests a key role for O-GlcNAc in signal transduction pathways. Modulation of O-GlcNAc levels has profound effects on the functioning of cells, in part mediated through a complex interplay between O-GlcNAc and O-phosphate. In many well-studied proteins, the O-GlcNAc modification and phosphorylation are reciprocal. That is, they occur on different subsets of the protein population, as the site of attachment occurs on the same or adjacent Ser/Thr residues. Recently, O-GlcNAc has been implicated in the etiology of type II diabetes, the regulation of stress response pathways, and in the regulation of the proteasome.",
keywords = "BAG, benzyl-α-GalNAc, C-terminal domain, casein kinase II, CK II, CTD, endothelial nitric oxide synthase, eNOS, ER, ERK, estrogen receptor, Heat shock, Hyperglycemia, N-acetylglucosamine, O-GlcNAc, Phosphorylation, Post-translational modification, Stress",
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AU - Hart, Gerald Warren

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AB - Myriad nuclear and cytoplasmic proteins in metazoans are modified on Ser and Thr residues by the monosaccharide O-linked β-N-acetylglucosamine (O-GlcNAc). The rapid and dynamic change in O-GlcNAc levels in response to extracellular stimuli, morphogens, the cell cycle and development suggests a key role for O-GlcNAc in signal transduction pathways. Modulation of O-GlcNAc levels has profound effects on the functioning of cells, in part mediated through a complex interplay between O-GlcNAc and O-phosphate. In many well-studied proteins, the O-GlcNAc modification and phosphorylation are reciprocal. That is, they occur on different subsets of the protein population, as the site of attachment occurs on the same or adjacent Ser/Thr residues. Recently, O-GlcNAc has been implicated in the etiology of type II diabetes, the regulation of stress response pathways, and in the regulation of the proteasome.

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