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Cited by 299

The DOI matches its Crossref record; 45 of the 45 references it cites were found in a registry or an index.

Exploring the O -GlcNAc proteome: Direct identification of O -GlcNAc-modified proteins from the brain

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Khidekel, Nelly, Ficarro, Scott B., Peters, Eric C., Hsieh-Wilson, Linda C.·2004·Proceedings of the National Academy of Sciences

Abstract

The covalent modification of intracellular proteins by O -linked β- N -acetylglucosamine ( O -GlcNAc) is emerging as a crucial regulatory posttranslational modification akin to phosphorylation. Numerous studies point to the significance of O -GlcNAc in cellular processes such as nutrient sensing, protein degradation, and gene expression. Despite its importance, the breadth and functional roles of O -GlcNAc are only beginning to be elucidated. Advances in our understanding will require the development of new strategies for the detection and study of O -GlcNAc-modified proteins in vivo . Herein we report the direct, high-throughput analysis of O -GlcNAc-glycosylated proteins from the mammalian brain. The proteins were identified by using a chemoenzymatic approach that exploits an engineered galactosyltransferase enzyme to selectively label O -GlcNAc proteins with a ketone-biotin tag. The tag permits enrichment of low-abundance O -GlcNAc species from complex mixtures and localization of the modification to short amino acid sequences. Using this approach, we discovered 25 O -GlcNAc-glycosylated proteins from the brain, including regulatory proteins associated with gene expression, neuronal signaling, and synaptic plasticity. The functional diversity represented by this set of proteins suggests an expanded role for O -GlcNAc in regulating neuronal function. Moreover, the chemoenzymatic strategy described here should prove valuable for identifying O -GlcNAc-modified proteins in various tissues and facilitate studies of the physiological significance of O -GlcNAc across the proteome.

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Metadata

Authors
Khidekel, N., Ficarro, S. B., Peters, E. C., & Hsieh-Wilson, L. C.
Venue
Proceedings of the National Academy of Sciences
Published
2004-08-30
Volume
101
Issue
36
Pages
13132-13137
ISSN
  • 0027-8424 (ISSN-L)
  • 1091-6490
OpenAlex
W2149202312
Cited by
299
References
45
FWCI
5.47
Type
journal article
Language
en
Open access
green

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Khidekel, N., Ficarro, S. B., Peters, E. C., & Hsieh-Wilson, L. C. (2004). Exploring the O -GlcNAc proteome: Direct identification of O -GlcNAc-modified proteins from the brain. Proceedings of the National Academy of Sciences. https://doi.org/10.1073/pnas.0403471101

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