O-GlcNAcylation is a post-translational modification of proteins that involves the addition of O-GlcNAc to serine or threonine residues of nuclear or cytoplasmic proteins, catalyzed by O-GlcNAc transferase (OGT). This modification is highly dynamic and can be reversed by O-GlcNAcase (OGA). O-GlcNAcylation is widespread in the immune system, which engages in multiple physiologic and pathophysiologic processes. There is substantial evidence indicating that both the hexosamine biosynthesis pathway (HBP) and O-GlcNAcylation are critically involved in regulating immune cell function. However, the precise role of O-GlcNAcylation in the immune system needs to be adequately elucidated. This review offers a thorough synopsis of the present research on protein O-GlcNAcylation, accentuating the molecular mechanisms that control immune cells' growth, maturation, and performance this PTM.
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http://dx.doi.org/10.3389/fimmu.2023.1209970 | DOI Listing |
Bioinformatics
January 2025
Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, United States.
Motivation: The accurate prediction of O-GlcNAcylation sites is crucial for understanding disease mechanisms and developing effective treatments. Previous machine learning models primarily relied on primary or secondary protein structural and related properties, which have limitations in capturing the spatial interactions of neighboring amino acids. This study introduces local environmental features as a novel approach that incorporates three-dimensional spatial information, significantly improving model performance by considering the spatial context around the target site.
View Article and Find Full Text PDFChembiochem
January 2025
Khon Kaen University, Biochemistry, Medicine, 123 Moo 16, 40002, Khon Kaen, THAILAND.
O-GlcNAcylation is an important biological process in regulating the function of many nucleocytoplasmic proteins in cells. Enhancement of O-GlcNAcylation was associated with cancer development and progression. Here, we demonstrated the involvement of O-GlcNAcylation in melanoma metastasis.
View Article and Find Full Text PDFJ Chem Inf Model
January 2025
Department of Chemistry, Faculty of Science, University of Waterloo, Waterloo, Ontario N2L 3G1, Canada.
Tau is a microtubule (MT)-associated protein that binds to and stabilizes the MTs of neurons. Due to its intrinsically disordered nature, it undergoes several post-translational modifications (PTMs) that are intricately linked to both the physiological and pathophysiological roles of Tau. Prior research has shown phosphorylation and O-GlcNAcylation to have contrasting effects on Tau aggregation; however, the precise molecular mechanisms and potential synergistic effects of these modifications remain elusive.
View Article and Find Full Text PDFAm J Physiol Cell Physiol
January 2025
Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro.
O-GlcNAcylation is a post-translational modification characterized by the covalent attachment of a single moiety of GlcNAc on serine/threonine residues in proteins. Tyrosine hydroxylase (TH), the rate-limiting step enzyme in the catecholamine synthesis pathway and responsible for production of the dopamine precursor, L-DOPA, has its activity regulated by phosphorylation. Here, we show an inverse feedback mechanism between O-GlcNAcylation and phosphorylation of TH at serine 40 (TH pSer40).
View Article and Find Full Text PDFAdv Sci (Weinh)
January 2025
Department of Pharmacology and Chemical Biology, Emory University School of Medicine, Atlanta, GA, 30322, USA.
Triple-negative breast cancer (TNBC) in obese patients remains challenging. Recent studies have linked obesity to an increased risk of TNBC and malignancies. Through multiomic analysis and experimental validation, a dysfunctional Eukaryotic Translation Initiation Factor 3 Subunit H (EIF3H)/Yes-associated protein (YAP) proteolytic axis is identified as a pivotal junction mediating the interplay between cancer-associated adipocytes and the response to anti-cancer drugs in TNBC.
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