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Cited by 1,317Glycosylation and Glycoproteins ResearchCarbohydrate Chemistry and SynthesisRedox biology and oxidative stress

Cross Talk Between O-GlcNAcylation and Phosphorylation: Roles in Signaling, Transcription, and Chronic Disease

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Hart, Gerald W., Slawson, Chad, Ramirez-Correa, Genaro, Lagerlof, Olof·2011·Annual Review of Biochemistry
DOI 10.1146/annurev-biochem-060608-102511PMC PMC3294376
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Abstract

O-GlcNAcylation is the addition of β-D-N-acetylglucosamine to serine or threonine residues of nuclear and cytoplasmic proteins. O-linked N-acetylglucosamine (O-GlcNAc) was not discovered until the early 1980s and still remains difficult to detect and quantify. Nonetheless, O-GlcNAc is highly abundant and cycles on proteins with a timescale similar to protein phosphorylation. O-GlcNAc occurs in organisms ranging from some bacteria to protozoans and metazoans, including plants and nematodes up the evolutionary tree to man. O-GlcNAcylation is mostly on nuclear proteins, but it occurs in all intracellular compartments, including mitochondria. Recent glycomic analyses have shown that O-GlcNAcylation has surprisingly extensive cross talk with phosphorylation, where it serves as a nutrient/stress sensor to modulate signaling, transcription, and cytoskeletal functions. Abnormal amounts of O-GlcNAcylation underlie the etiology of insulin resistance and glucose toxicity in diabetes, and this type of modification plays a direct role in neurodegenerative disease. Many oncogenic proteins and tumor suppressor proteins are also regulated by O-GlcNAcylation. Current data justify extensive efforts toward a better understanding of this invisible, yet abundant, modification. As tools for the study of O-GlcNAc become more facile and available, exponential growth in this area of research will eventually take place.

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  • There seems to be a limited number of forms of intracellular glycosylation, with O-GlcNAc numerically dominating.

    “there seems to be a limited number of forms of intracellular glycosylation, with a single modi fi cation ( O -GlcNAc) numerically dominating the scene (647 -648).”

    From Biological roles of glycans (2017) · cites this paper as [648]

    The Introduction (page not provided) says O-GlcNAc occurs in most intracellular compartments and is known on over a thousand proteins, supporting its abundance. It does not say that forms of intracellular glycosylation are limited or compare their numbers to establish that O-GlcNAc dominates. (LLM, conf=0.82)

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Research works printed but not linked: 7

  1. [46]Cieniewski-Bernard C Bastide B Lefebvre T Lemoine J Mounier Y Michalski JC 2004 Identification of O-linked N-acetylglucosamine proteins in rat skeletal muscle using two-dimensional gel electrophoresis and mass spectrometry Mol Cell Proteomics 3 577 85 14985449
  2. [77]Cheung WD Sakabe K Housley MP Dias WB Hart GW 2008 O-GlcNAc transferase substrate specificity is regulated by MYPT1 and other interacting proteins J Biol Chem 283 33935 41 18840611 PMC2590692
  3. [79]Housley MP Udeshi ND Rodgers JT Shabanowitz J Puigserver P 2009 A PGC-1alpha-O-GlcNAc transferase complex regulates FoxO transcription factor activity in response to glucose J Biol Chem 284 5148 57 19103600 PMC2643526
  4. [114]Wang Z Udeshi ND Slawson C Compton PD Sakabe K 2010 Extensive crosstalk between O-GlcNAcylation and phosphorylation regulates cytokinesis Sci Signal 3 ra2 20068230 PMC2866299
  5. [128]Wells L Kreppel LK Comer FI Wadzinski BE Hart GW 2004 O-GlcNAc transferase is in a functional complex with protein phosphatase 1 catalytic subunits J Biol Chem 279 38466 70 15247246
  6. [162]Ramirez-Correa GA Jin W Wang Z Zhong X Gao WD 2008 O-linked GlcNAc modification of cardiac myofilament proteins. A novel regulator of myocardial contractile function Circ Res 103 1354 58 18988896 PMC2615199
  7. [198]Arnold CS Johnson GV Cole RN Dong DL Lee M Hart GW 1996 The microtubule-associated protein tau is extensively modified with O-linked N-acetylglucosamine J Biol Chem 271 28741 44 8910513

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Authors
Hart, G. W., Slawson, C., Ramirez-Correa, G., & Lagerlof, O.
Affiliations
  • Johns Hopkins University (US)
  • Departments of Biological Chemistry, Johns Hopkins University, School of Medicine, Baltimore, Maryland 21205;, cslawso1@jhmi.edu, gramire2@jhmi.edu, olof.lagerlof@gmail.com
  • Departments of Biological Chemistry and Pediatrics, Johns Hopkins University, School of Medicine, Baltimore, Maryland 21205;
ORCID
Venue
Annual Review of Biochemistry
Publisher
Annual Reviews
Published
2011-07-07
Volume
80
Issue
1
Pages
825-858
ISSN
  • 0066-4154 (ISSN-L)
  • 1545-4509
DOI
10.1146/annurev-biochem-060608-102511
PMC
PMC3294376
OpenAlex
W2140409722
Cited by
1,317
References
235
Citations by year
2026: 65 · 2025: 75 · 2024: 88 · 2023: 73 · 2022: 92 · 2021: 121 · 2020: 83 · 2019: 78 · 2018: 90 · 2017: 87 · 2016: 88 · 2015: 91 · 2014: 122 · 2013: 95 · 2012: 53
FWCI
8.27
Type
journal article
Language
en
Open access
Locations
  • Annual Review of Biochemistry (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
  • ScholarWorks @ UTRGV (The University of Texas Rio Grande Valley) (submittedVersion)
Funders
  • National Institutes of Health (4r33dk071280-03)
  • National Cancer Institute (R01CA42486, R01CA042486)
  • National Institute of Diabetes and Digestive and Kidney Diseases (R01DK061671, R33-DK-071280, R24DK084949, P30DK079637, R33 DK071280-04, R01-DK61671)
  • Eunice Kennedy Shriver National Institute of Child Health and Human Development (R37HD013563)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Glycosylation and Glycoproteins Research
  • Physical Sciences › Chemistry › Organic Chemistry › Carbohydrate Chemistry and Synthesis
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
Keywords
O-GlcNAcylation, protein phosphorylation, post-translational modification, O-GlcNAc transferase, O-GlcNAcase, protein glycosylation, nutrient sensing, stress sensing, signal transduction, transcriptional regulation, cytoskeleton, mitochondria, insulin resistance, glucotoxicity, diabetes mellitus, neurodegenerative diseases, oncoprotein, tumor suppressor proteins, chronic disease
MeSH terms
Acetylglucosamine, Animals, Chronic Disease, Diabetes Mellitus, Glycosylation, Humans, Models, Molecular, Neoplasms, Phosphorylation, Protein Conformation, Transcription, Genetic, Molecular Structure, Signal Transduction, N-Acetylglucosaminyltransferases, Neurodegenerative Diseases

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