Three decades of research on O-GlcNAcylation - A major nutrient sensor that regulates signaling, transcription and cellular metabolism

Gerald Warren Hart

Research output: Contribution to journalArticle

Abstract

Even though the dynamic modification of polypeptides by the monosaccharide, O-linked N-acetylglucosamine (O-GlcNAcylation) was discovered over 30 years ago, its physiological significance as a major nutrient sensor that regulates myriad cellular processes has only recently been more widely appreciated. O-GlcNAcylation, either on its own or by its interplay with other post-translational modifications, such as phosphorylation, ubiquitination, and others, modulates the activities of signaling proteins, regulates most components of the transcription machinery, affects cell cycle progression and regulates the targeting/turnover or functions of myriad other regulatory proteins, in response to nutrients. Acute increases in O-GlcNAcylation protect cells from stress-induced injury, while chronic deregulation of O-GlcNAc cycling contributes to the etiology of major human diseases of aging, such as diabetes, cancer, and neurodegeneration. Recent advances in tools to study O-GlcNAcylation at the individual site level and specific inhibitors of O-GlcNAc cycling have allowed more rapid progress toward elucidating the specific functions of O-GlcNAcylation in essential cellular processes.

Original languageEnglish (US)
Article number183
JournalFrontiers in Endocrinology
Volume5
Issue numberOCT
DOIs
StatePublished - 2014

Keywords

  • Alzheimer's disease
  • Cancer
  • Diabetes
  • O-GlcNAc transferase
  • O-GlcNAcase
  • O-GlcNAcylation
  • Signaling
  • Transcription

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism

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