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Journal article
Activation of the Transcriptional Function of the NF-kappa B Protein c-Rel by O-GlcNAc Glycosylation
Science signaling, v 6(290), pp ra75-ra75
27 Aug 2013
PMID: 23982206
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
The transcription factor nuclear factor kappa B (NF-kappa B) rapidly reprograms gene expression in response to various stimuli, and its activity is regulated by several posttranslational modifications, including phosphorylation, methylation, and acetylation. The addition of O-linked beta-N-acetylglucosamine (a process known as O-GlcNAcylation) is an abundant posttranslational modification that is enhanced in conditions such as hyperglycemia and cellular stress. We report that the NF-kappa B subunit c-Rel is modified and activated by O-GlcNAcylation. We identified serine 350 as the site of O-GlcNAcylation, which was required for the DNA binding and transactivation functions of c-Rel. Blocking the O-GlcNAcylation of this residue abrogated c-Rel-mediated expression of the cytokine-encoding genes IL2, IFNG, and CSF2 in response to T cell receptor (TCR) activation, whereas increasing the extent of O-GlcNAcylation of cellular proteins enhanced the expression of these genes. TCR-or tumor necrosis factor (TNF)-induced expression of other NF-kappa B target genes, such as NFKBIA (which encodes I kappa B alpha) and TNFAIP3 (which encodes A20), occurred independently of the O-GlcNAcylation of c-Rel. Our findings suggest a stimulus-specific role for hyperglycemia-induced O-GlcNAcylation of c-Rel in promoting T cell-mediated autoimmunity in conditions such as type 1 diabetes by enhancing the production of T helper cell cytokines.
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Details
- Title
- Activation of the Transcriptional Function of the NF-kappa B Protein c-Rel by O-GlcNAc Glycosylation
- Creators
- Parameswaran Ramakrishnan - California Institute of TechnologyPeter M. Clark - California Institute of TechnologyDaniel E. Mason - Genomics Institute of the Novartis Research FoundationEric C. Peters - Genomics Institute of the Novartis Research FoundationLinda C. Hsieh-Wilson - California Institute of TechnologyDavid Baltimore - California Institute of Technology
- Publication Details
- Science signaling, v 6(290), pp ra75-ra75
- Publisher
- Amer Assoc Advancement Science
- Number of pages
- 13
- Grant note
- 2R01 GM039458; 2RO1 GM084724 / NIH; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA R01GM084724 / NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of General Medical Sciences (NIGMS) Mizutani Foundation for Glycoscience grant
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- School of Biomedical Engineering, Science, and Health Systems; Drexel University
- Web of Science ID
- WOS:000323707200004
- Scopus ID
- 2-s2.0-84884139186
- Other Identifier
- 991019356498504721
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- Collaboration types
- Industry collaboration
- Domestic collaboration
- Web of Science research areas
- Biochemistry & Molecular Biology
- Cell Biology