Modulation of extrinsic apoptotic pathway by intracellular glycosylation

• Published in: Trends in cell biology 2024-09, Vol.34 (9), p.728-741
• Main Authors: Seyrek, Kamil, Ivanisenko, Nikita V., König, Corinna, Lavrik, Inna N.
• Format: Article
• Language: English
• Subjects: Acetylglucosamine - metabolism; Animals; Apoptosis; Glycosylation; Humans; N-Acetylglucosaminyltransferases - metabolism; NleB; O-GlcNAcylation; OGA; OGT; Protein Processing, Post-Translational; Signal Transduction; SseK
• ISSN: 0962-8924; 1879-3088; 1879-3088
• DOI: 10.1016/j.tcb.2024.01.003

O-GlcNAcylation of intracellular proteins takes place via a single transfer of GlcNAc to the hydroxyl group of serine or threonine residues.O-GlcNAcylation modulates the extrinsic apoptotic pathway.To facilitate colonization of pathogens in host cells, bacterial effector proteins suppress death receptor (DR) signaling.Sustained increases in O-GlcNAcylation contribute to tumor development. The importance of post-translational modifications (PTMs), particularly O-GlcNAcylation, of cytoplasmic proteins in apoptosis has been neglected for quite a while. Modification of cytoplasmic proteins by a single N-acetylglucosamine sugar is a dynamic and reversible PTM exhibiting properties more like phosphorylation than classical O- and N-linked glycosylation. Due to the sparse information existing, we have only limited understanding of how GlcNAcylation affects cell death. Deciphering the role of GlcNAcylation in cell fate may provide further understanding of cell fate decisions. This review focus on the modulation of extrinsic apoptotic pathway via GlcNAcylation carried out by O-GlcNAc transferase (OGT) or by other bacterial effector proteins. The importance of post-translational modifications (PTMs), particularly O-GlcNAcylation, of cytoplasmic proteins in apoptosis has been neglected for quite a while. Modification of cytoplasmic proteins by a single N-acetylglucosamine sugar is a dynamic and reversible PTM exhibiting properties more like phosphorylation than classical O- and N-linked glycosylation. Due to the sparse information existing, we have only limited understanding of how GlcNAcylation affects cell death. Deciphering the role of GlcNAcylation in cell fate may provide further understanding of cell fate decisions. This review focus on the modulation of extrinsic apoptotic pathway via GlcNAcylation carried out by O-GlcNAc transferase (OGT) or by other bacterial effector proteins.