The Biochemistry of O-GlcNAc Transferase: Which Functions Make It Essential in Mammalian Cells?

Abstract

O-linked N-acetylglucosamine transferase (OGT) is found in all metazoans and plays an important role in development but at the single-cell level is only essential in dividing mammalian cells. Postmitotic mammalian cells and cells of invertebrates such as Caenorhabditis elegans and Drosophila can survive without copies of OGT. Why OGT is required in dividing mammalian cells but not in other cells remains unknown. OGT has multiple biochemical activities. Beyond its well-known role in adding β-O-GlcNAc to serine and threonine residues of nuclear and cytoplasmic proteins, OGT also acts as a protease in the maturation of the cell cycle regulator host cell factor 1 (HCF-1) and serves as an integral member of several protein complexes, many of them linked to gene expression. In this review, we summarize current understanding of the mechanisms underlying OGT's biochemical activities and address whether known functions of OGT could be related to its essential role in dividing mammalian cells.

Protein O-GlcNAcylation: emerging mechanisms and functions

“…Here, we consider potential mechanisms enabling recognition of hundreds of protein substrates by a single OGT and OGA; discuss how O -GlcNAcylation regulates cellular processes temporally and spatially in response to nutritional and hormonal cues; and explore how O -GlcNAc homeostasis may be maintained in order to achieve optimal cellular function. Since there are already many comprehensive reviews describing the diverse functions of O -GlcNAcylation, the focus of this Review is on consolidating this knowledge into unifying concepts, with an emphasis on contextualizing the significant advances the field has seen over the past several years 1, 2, 4, 6, 10–12 .…”

O-GlcNAc Transferase Links Glucose Metabolism to MAVS-Mediated Antiviral Innate Immunity

“…HBP has been considered as a minor glucose metabolism pathway, since only 2–5% of the glucose that enters cells is directed to this pathway, eventually leading to the generation of its end product uridine diphosphate N-acetylglucosamine (UDP-GlcNAc) (Hardiville and Hart, 2014). O -GlcNAc transferase (OGT) mediates the transfer of UDP-GlcNAc to serine or threonine residue of target proteins, known as protein O -GlcNAcylation (Levine and Walker, 2016; Yang and Qian, 2017). Previous studies have discovered essential roles of HBP and protein O- GlcNAcylation in many fundamental biological activities (Bond and Hanover, 2013; Hart et al, 2011).…”

Nuclear factor-erythroid-2 related transcription factor-1 (Nrf1) is regulated by O-GlcNAc transferase

“…OGT is able to associate with a diverse group of proteins through its TPR domain that mediates protein-protein interactions with numerous accessory proteins [10][11][12][13]. These accessory proteins include HCF1, TET proteins, TRAK1, BAP1, among others [14]. Interestingly, OGT also acts as a protease that catalyzes the cleavage and maturation of Host Cell Factor-1 (HCF1) [15].…”