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Integration of O-GlcNAc into Stress Response Pathways

Kamau M M Fahie1, Kyriakos N Papanicolaou2, Natasha E Zachara1,3

  • 1Department of Biological Chemistry, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.

Cells
|November 11, 2022
PubMed

Insights

O-linked βN-acetylglucosamine (O-GlcNAc) is a key protein modification that regulates cellular responses to stress. This process is vital for cell survival during various injuries, particularly in the cardiovascular and nervous systems.

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Cellular Biology

Background:

  • O-linked βN-acetylglucosamine (O-GlcNAc) is a dynamic post-translational modification found on thousands of mammalian proteins.
  • O-GlcNAc cycling influences fundamental cellular processes including epigenetics, transcription, translation, proteostasis, metabolism, and signal transduction.

Purpose of the Study:

  • To explore the integration of O-GlcNAc modification into cellular stress response pathways.
  • To highlight the role of O-GlcNAc in cellular and tissue survival under various injury conditions.
  • To focus on the specific functions of O-GlcNAc in the cardiovascular system and neurodegeneration.

Main Methods:

  • Review of existing literature on O-GlcNAc modification and cellular stress.
  • Analysis of O-GlcNAc's impact on protein function and cellular pathways.
  • Examination of O-GlcNAc's role in models of physiological and environmental injury.

Main Results:

  • O-GlcNAcylation is altered by diverse stimuli and plays a critical role in cell survival during heat shock, osmotic stress, oxidative stress, and hypoxia.
  • Mechanisms of O-GlcNAc-mediated survival involve modulation of chaperone levels, unfolded protein response, mitochondrial function, and protein aggregation.
  • O-GlcNAc modification is intricately linked to cellular defense mechanisms against various forms of stress.

Conclusions:

  • O-GlcNAc is a crucial regulator of the cellular stress response, impacting cell and tissue survival.
  • Understanding O-GlcNAc's role is essential for developing therapeutic strategies for cardiovascular diseases and neurodegenerative disorders.
  • Further research into O-GlcNAc pathways can uncover novel targets for treating stress-related conditions.
Keywords:
O-GlcNAcchaperoneglycosylationstress

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