Modulation of transcription factor function by O-GlcNAc modification.
O-linked beta-N-acetylglucosamine (O-GlcNAc) modification of nuclear and cytoplasmic proteins is important for many cellular processes, and the number of proteins that contain this modification is steadily increasing. This modification is dynamic and reversible, and in some cases competes for phosphorylation of the same residues. O-GlcNAc modification of proteins is regulated by cell cycle, nutrient metabolism, and other extracellular signals. Compared to protein phosphorylation, which is mediated by a large number of kinases, O-GlcNAc modification is catalyzed only by one enzyme called O-linked N-acetylglucosaminyl transferase or OGT. Removal of O-GlcNAc from proteins is catalyzed by the enzyme beta-N-acetylglucosaminidase (O-GlcNAcase or OGA). Altered O-linked GlcNAc modification levels contribute to the establishment of many diseases, such as cancer, diabetes, cardiovascular disease, and neurodegeneration. Many transcription factors have been shown to be modified by O-linked GlcNAc modification, which can influence their transcriptional activity, DNA binding, localization, stability, and interaction with other co-factors. This review focuses on modulation of transcription factor function by O-linked GlcNAc modification.
Ozcan
Sabire
S
Department of Molecular and Cellular Biochemistry, University of Kentucky, Lexington, KY 40536, USA. sozcan@uky.edu
Andrali
Sreenath S
SS
Cantrell
Jamie E L
JE
D000117:Acetylglucosamine / Q000737:chemistry* / Q000378:metabolism*; D021581:Active Transport, Cell Nucleus; D000818:Animals; D017362:Cyclic AMP Response Element-Binding Protein / Q000737:chemistry / Q000378:metabolism; D006031:Glycosylation; D006801:Humans; D008954:Models, Biological; D017351:N-Acetylglucosaminyltransferases / Q000378:metabolism; D016328:NF-kappa B / Q000737:chemistry / Q000378:metabolism; D054730:Protein Interaction Domains and Motifs; D011499:Protein Processing, Post-Translational; D055550:Protein Stability; D011960:Receptors, Estrogen / Q000737:chemistry / Q000378:metabolism; D050799:STAT5 Transcription Factor / Q000737:chemistry / Q000378:metabolism; D015534:Trans-Activators / Q000737:chemistry / Q000378:metabolism; D014157:Transcription Factors / Q000737:chemistry* / Q000378:metabolism*; D016159:Tumor Suppressor Protein p53 / Q000737:chemistry / Q000378:metabolism; D050986:YY1 Transcription Factor / Q000737:chemistry / Q000378:metabolism; D001619:beta-N-Acetylhexosaminidases / Q000378:metabolism
D017362:Cyclic AMP Response Element-Binding Protein; D016328:NF-kappa B; D011960:Receptors, Estrogen; D050799:STAT5 Transcription Factor; D015534:Trans-Activators; D014157:Transcription Factors; D016159:Tumor Suppressor Protein p53; D050986:YY1 Transcription Factor; D017351:N-Acetylglucosaminyltransferases; C449880:O-GlcNAc transferase; C110628:hexosaminidase C; D001619:beta-N-Acetylhexosaminidases; D000117:Acetylglucosamine