O-GlcNAcylation: Implications in normal and malignant hematopoiesis

• Published in: Experimental hematology Vol. 101-102; pp. 16 - 24
• Main Authors: Nakajima, Hideaki, Murakami, Koichi
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Inc 01.09.2021
• Subjects: Acetylglucosamine - genetics; Acetylglucosamine - metabolism; Animals; Epigenesis, Genetic; Hematologic Neoplasms - genetics; Hematologic Neoplasms - metabolism; Hematologic Neoplasms - pathology; Hematopoiesis; Hematopoietic Stem Cells - metabolism; Hematopoietic Stem Cells - pathology; Humans; Protein Processing, Post-Translational
• ISSN: 0301-472X; 1873-2399
• DOI: 10.1016/j.exphem.2021.07.003

•O-GlcNAcylation is an evolutionarily conserved, reversible protein modification regulated by OGT and OGA.•O-GlcNAcylation regulates fundamental biological processes in diverse cell types by sensing extracellular state.•O-GlcNAcylation is critical for proliferation, differentiation, and homeostatic maintenance of hematopoietic cells.•Aberrant O-GlcNAcylation is implicated in pathogenesis of hematologic malignancies through epigenetic dysregulation. Posttranslational protein modification through addition of the O‐linked β-N-acetyl-D-glucosamine (O-GlcNAc) moiety to serine or threonine residues, termed O-GlcNAcylation, is a highly dynamic process conserved throughout eukaryotes. O-GlcNAcylation is reversibly catalyzed by a single pair of enzymes, O-GlcNAc transferase and O-GlcNAcase, and it acts as a fundamental regulator for a wide variety of biological processes including gene expression, cell cycle regulation, metabolism, stress response, cellular signaling, epigenetics, and proteostasis. O-GlcNAcylation is regulated by various intracellular or extracellular cues such as metabolic status, nutrient availability, and stress. Studies over decades have unveiled the profound biological significance of this unique protein modification in normal physiology and pathologic processes of diverse cell types or tissues. In hematopoiesis, recent studies have indicated the essential and pleiotropic roles of O-GlcNAcylation in differentiation, proliferation, and function of hematopoietic cells including T cells, B cells, myeloid progenitors, and hematopoietic stem and progenitor cells. Moreover, aberrant O-GlcNAcylation is implicated in the development of hematologic malignancies with dysregulated epigenetics, metabolism, and gene transcription. Thus, it is now recognized that O-GlcNAcylation is one of the key regulators of normal and malignant hematopoiesis.