{"doi":"10.1016/j.celrep.2024.114976","title":"O-GlcNAcylation modulates expression and abundance of N-glycosylation machinery in an inherited glycosylation disorder","abstract":"Core components of the N-glycosylation pathway are known, but the metabolic and post-translational mechanisms regulating this pathway in normal and disease states remain elusive. Using a multi-omic approach in zebrafish, we discovered a mechanism whereby O-GlcNAcylation directly impacts the expression and abundance of two rate-limiting proteins in the N-linked glycosylation pathway. We show in a model of an inherited glycosylation disorder PMM2-CDG, congenital disorders of glycosylation that phosphomannomutase deficiency is associated with increased levels of UDP-GlcNAc and protein O-GlcNAcylation. O-GlcNAc modification increases the transcript and protein abundance of both NgBR and Dpagt1 in pmm2 m/m mutants. Modulating O-GlcNAc levels, NgBR abundance, or Dpagt1 activity exacerbated the cartilage phenotypes in pmm2 mutants, suggesting that O-GlcNAc-mediated increases in the N-glycosylation machinery are protective. These findings highlight nucleotide-sugar donors as metabolic sensors that regulate two spatially separated glycosylation pathways, demonstrating how their coordination is relevant to disease severity in the most common congenital disorder of glycosylation.","journal":"Cell Reports","year":2024,"id":429277,"datarank":0.3866064131476575,"base_score":2.3978952727983707,"endowment":2.3978952727983707,"self_citation_contribution":0.3596842909197557,"citation_network_contribution":0.026922122227901784,"self_endowment_contribution":0.3596842909197557,"citer_contribution":0.026922122227901784,"corpus_percentile":null,"corpus_rank":null,"citation_count":10,"citer_count":9,"citers_with_citation_signal":3,"citers_with_endowment":3,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9515,"is_data_producer":true,"deposit_databanks":{"GEO":["GSE269074"]},"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":711606,"name":"Sneha S. Mokashi","orcid":"0000-0002-0981-5877","position":1,"is_corresponding":false},{"id":314218,"name":"Silvia Radenkovic","orcid":"0000-0001-8190-7736","position":2,"is_corresponding":false},{"id":1231929,"name":"Kali Wiggins","orcid":null,"position":3,"is_corresponding":false},{"id":776602,"name":"Lynn Dukes‐Rimsky","orcid":null,"position":4,"is_corresponding":false},{"id":377097,"name":"Peggi M. Angel","orcid":"0000-0002-4436-555X","position":5,"is_corresponding":false},{"id":228140,"name":"Bart Ghesquière","orcid":"0000-0003-1547-1705","position":6,"is_corresponding":false},{"id":355553,"name":"Tamás Kozicz","orcid":"0000-0001-6915-4364","position":7,"is_corresponding":false},{"id":390579,"name":"Richard Steet","orcid":"0000-0002-0975-4963","position":8,"is_corresponding":false},{"id":314243,"name":"Éva Morava","orcid":"0000-0001-7441-700X","position":9,"is_corresponding":false},{"id":390578,"name":"Heather Flanagan‐Steet","orcid":"0000-0001-8295-0453","position":10,"is_corresponding":false},{"id":1231928,"name":"Courtney Matheny-Rabun","orcid":null,"position":0,"is_corresponding":true}],"reference_count":58,"raw_metadata":null,"created_at":"2026-07-19T01:59:06.668462Z","pmid":"39561044","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":[]}