TY - JOUR
T1 - Three decades of research on O-GlcNAcylation - A major nutrient sensor that regulates signaling, transcription and cellular metabolism
AU - Hart, Gerald Warren
PY - 2014
Y1 - 2014
N2 - 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.
AB - 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.
KW - Alzheimer's disease
KW - Cancer
KW - Diabetes
KW - O-GlcNAc transferase
KW - O-GlcNAcase
KW - O-GlcNAcylation
KW - Signaling
KW - Transcription
UR - http://www.scopus.com/inward/record.url?scp=84926686351&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84926686351&partnerID=8YFLogxK
U2 - 10.3389/fendo.2014.00183
DO - 10.3389/fendo.2014.00183
M3 - Article
C2 - 25386167
AN - SCOPUS:84926686351
SN - 1664-2392
VL - 5
JO - Frontiers in Endocrinology
JF - Frontiers in Endocrinology
IS - OCT
M1 - 183
ER -