TY - JOUR
T1 - Roles of O-GlcNAc in chronic diseases of aging
AU - Banerjee, Partha S.
AU - Lagerlöf, Olof
AU - Hart, Gerald W.
N1 - Funding Information:
The authors are supported by NIH grants R01DK61671 , P01HL107153 , and N01-HV-00240 . G.W.H. receives a share of royalties received by Johns Hopkins University (JHU) on sales of the CTD 110.6 antibody, which are managed by JHU. We would like to thank Dr. S.B. Peterson and Dr. S. Hardiville for critical reading of the manuscript.
Publisher Copyright:
© 2016 Elsevier Ltd
PY - 2016/10/1
Y1 - 2016/10/1
N2 - O-GlcNAcylation, a dynamic nutrient and stress sensitive post-translational modification, occurs on myriad proteins in the cell nucleus, cytoplasm and mitochondria. O-GlcNAcylation serves as a nutrient sensor to regulate signaling, transcription, translation, cell division, metabolism, and stress sensitivity in all cells. Aberrant protein O-GlcNAcylation plays a critical role both in the development, as well as in the progression of a variety of age related diseases. O-GlcNAcylation underlies the etiology of diabetes, and changes in specific protein O-GlcNAc levels and sites are responsible for insulin expression and sensitivity and glucose toxicity. Abnormal O-GlcNAcylation contributes directly to diabetes related dysfunction of the heart, kidney and eyes and affects progression of cardiomyopathy, nephropathy and retinopathy. O-GlcNAcylation is a critical modification in the brain and plays a role in both plaque and tangle formation, thus making its study important in neurodegenerative disorders. O-GlcNAcylation also affects cellular growth and metabolism during the development and metastasis of cancer. Finally, alterations in O-GlcNAcylation of transcription factors in macrophages and lymphocytes affect inflammation and cytokine production. Thus, O-GlcNAcylation plays key roles in many of the major diseases associated with aging. Elucidation of its specific functions in both normal and diseased tissues is likely to uncover totally novel avenues for therapeutic intervention.
AB - O-GlcNAcylation, a dynamic nutrient and stress sensitive post-translational modification, occurs on myriad proteins in the cell nucleus, cytoplasm and mitochondria. O-GlcNAcylation serves as a nutrient sensor to regulate signaling, transcription, translation, cell division, metabolism, and stress sensitivity in all cells. Aberrant protein O-GlcNAcylation plays a critical role both in the development, as well as in the progression of a variety of age related diseases. O-GlcNAcylation underlies the etiology of diabetes, and changes in specific protein O-GlcNAc levels and sites are responsible for insulin expression and sensitivity and glucose toxicity. Abnormal O-GlcNAcylation contributes directly to diabetes related dysfunction of the heart, kidney and eyes and affects progression of cardiomyopathy, nephropathy and retinopathy. O-GlcNAcylation is a critical modification in the brain and plays a role in both plaque and tangle formation, thus making its study important in neurodegenerative disorders. O-GlcNAcylation also affects cellular growth and metabolism during the development and metastasis of cancer. Finally, alterations in O-GlcNAcylation of transcription factors in macrophages and lymphocytes affect inflammation and cytokine production. Thus, O-GlcNAcylation plays key roles in many of the major diseases associated with aging. Elucidation of its specific functions in both normal and diseased tissues is likely to uncover totally novel avenues for therapeutic intervention.
KW - Cancer
KW - Diabetes
KW - Hexosamine biosynthetic pathway
KW - Hyperglycemia
KW - Neurodegenerative disease
KW - O-GlcNAc
KW - O-GlcNAc transferase
KW - O-GlcNAcase
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U2 - 10.1016/j.mam.2016.05.005
DO - 10.1016/j.mam.2016.05.005
M3 - Review article
C2 - 27259471
AN - SCOPUS:84973161413
SN - 0098-2997
VL - 51
SP - 1
EP - 15
JO - Molecular Aspects of Medicine
JF - Molecular Aspects of Medicine
ER -