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Complex Between GlcNAcylation & Phosphorylation is Extensive: Roles in Nutrient Sensing & Signaling
Author(s) -
Hart Gerald W.
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.24.1_supplement.303.2
Subject(s) - crosstalk , phosphorylation , kinase , signal transduction , rna polymerase ii , transcription factor , microbiology and biotechnology , biology , transcription (linguistics) , gene , chemistry , gene expression , biochemistry , promoter , physics , linguistics , philosophy , optics
O‐linked beta‐N‐acetylglucosamine (O‐GlcNAc) serves as a nutrient/stress sensor to modulate metabolic processes and gene expression (for review, Nature 446, 1017–1022; Am J Physiol Endocrinol Metab 295: E17–E28). O‐GlcNAc plays a direct role in the etiology of diabetes, neurodegenerative disease, and cancer. Recent phospho‐proteomic and glycomic studies have shown that the crosstalk between GlcNAcylation and phosphorylation is extensive at the individual site level. This dynamic interplay not only occurs by competition at the same or proximal sites, but also by each modification regulating the other's cycling enzymes. For example, several kinases are regulated by GlcNAcylation, and phosphorylation regulates both O‐GlcNAc Transferase and O‐GlcNAcase. The elucidation of this extensive crosstalk between these two most abundant protein modifications will have a major impact on our view of signaling and transcriptional regulation. Examples of the importance of this dynamic interplay in the regulation of FOXO transcription factors, kinases, RNA polymerase II, and cytokinesis will be presented. It is now clear that GlcNAcylation plays an important role in glucose toxcity and in insulin resistance. Dr. Hart receives a share of royalty received by the university on sales of the CTD 110.6 antibody. Terms of this arrangement are managed by JHUSOM.