{"doi":"10.1093/glycob/cwaf061","title":"The Glyco-Switch of life: O-GlcNAcylation in cell fate decision","abstract":"O-linked β-N-acetylglucosaminylation (O-GlcNAcylation) is a unique type of protein glycosylation that intricately links cellular metabolism to various signaling pathways. This reversible, nutrient-sensitive modification dynamically regulates a wide range of biological processes, including apoptosis, cell proliferation, and differentiation. Recent studies have made substantial progress in elucidating the pivotal roles of O-GlcNAcylation in modulating key oncogenes and signaling cascades. Aberrant O-GlcNAc cycling has been associated with a variety of pathological conditions, including cancer, metabolic disorders, and neurodegenerative diseases, underscoring its critical influence on cell fate decisions. In this review, we will highlight recent advances in understanding how O-GlcNAcylation modulates major cell fate regulating pathways, including nuclear factor kappaB (NF-κB), Notch, G protein-coupled receptor (GPCR) signaling, and transforming growth factor beta (TGF-β). We propose that O-GlcNAcylation integrates extracellular signals with intracellular metabolic states, functioning as an essential \"Glyco-Switch\" sensor that modulates cell fate decisions in both physiological and pathological contexts.","journal":"Glycobiology","year":2025,"id":580609,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9514,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1491786,"name":"Matthew T. Young","orcid":"0000-0001-5483-5036","position":1,"is_corresponding":false},{"id":404544,"name":"Jiaoyang Jiang","orcid":"0000-0001-8445-9924","position":2,"is_corresponding":false},{"id":404542,"name":"Ao Wang","orcid":"0000-0001-9560-9422","position":0,"is_corresponding":true}],"reference_count":146,"raw_metadata":null,"created_at":"2026-07-19T02:58:43.046112Z","pmid":"41206509","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}