Dynamic crosstalk between GlcAcylation and phosphorylation: Roles in signaling, transcription and human disease

Shino Shimoji, Kyoungsook Park, Gerald Warren Hart

Research output: Contribution to journalArticlepeer-review

Abstract

GlcNAcylation is a dynamic cytoplasmic and nuclear post-translational sugar modification of serine/threonine residues. The addition and removal of O-GlcNAc are regulated by O-GlcNAc Transferase and O-GlcNAcase, respectively. Over ~1000 proteins have been identified to be GlcNAcylated with over 240 mapped sites. O-GlcNAc is involved in critical cellular functions, such as cell-cycle regulation, apoptosis, stress responses, signaling, transcription, and translation. O-GlcNAc also plays pivotal roles in diseases, such as diabetes, neurodegenerative disease and cancer, and immunological regulation, such as T-cell activation. Through comparative proteomic analysis of resting and activated T-cells, we identified potentially GlcNAcylated proteins involved in post-signaling events of T-cell activation. O-GlcNAc on 58 proteins involved in processes, such as DNA replication, cytoskeletal rearrangement, chromatin remodeling, and RNA processing, were altered by T-cell activation. GlcNAcylation and phosphorylation are similar in abundance and cellular/ biological function, and their regulation is deeply intertwined. The two modifications regulate each other at the sitelevel by reciprocally influencing site-occupancy, and at the enzymatic-activity level by each modification modulating the catalytic activity of the enzymes involved in the other modification. This paper will focus on recent developments in the interplay between O-GlcNAc and phosphorylation, and O-GlcNAc's roles in human disease and immunology.

Original languageEnglish (US)
Pages (from-to)25-40
Number of pages16
JournalCurrent Signal Transduction Therapy
Volume5
Issue number1
DOIs
StatePublished - Jan 2010

Keywords

  • Crosstalk
  • Disease
  • GlcNAcylation
  • Lymphocyte
  • O-GlcNAc
  • Phosphorylation

ASJC Scopus subject areas

  • Endocrinology
  • Pharmacology (medical)

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