Glucose and glutamine fuel protein O-GlcNAcylation to control T cell self-renewal and malignancy View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2016-06

AUTHORS

Mahima Swamy, Shalini Pathak, Katarzyna M Grzes, Sebastian Damerow, Linda V Sinclair, Daan M F van Aalten, Doreen A Cantrell

ABSTRACT

Sustained glucose and glutamine transport are essential for activated T lymphocytes to support ATP and macromolecule biosynthesis. We found that glutamine and glucose also fuel an indispensable dynamic regulation of intracellular protein O-GlcNAcylation at key stages of T cell development, transformation and differentiation. Glucose and glutamine are precursors of uridine diphosphate N-acetylglucosamine (UDP-GlcNAc), a substrate for cellular glycosyltransferases. Immune-activated T cells contained higher concentrations of UDP-GlcNAc and increased intracellular protein O-GlcNAcylation controlled by the enzyme O-linked-β-N-acetylglucosamine (O-GlcNAc) glycosyltransferase as compared with naive cells. We identified Notch, the T cell antigen receptor and c-Myc as key controllers of T cell protein O-GlcNAcylation via regulation of glucose and glutamine transport. Loss of O-GlcNAc transferase blocked T cell progenitor renewal, malignant transformation and peripheral T cell clonal expansion. Nutrient-dependent signaling pathways regulated by O-GlcNAc glycosyltransferase are thus fundamental for T cell biology. More... »

PAGES

712-720

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/ni.3439

DOI

http://dx.doi.org/10.1038/ni.3439

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1033209585

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/27111141


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