{"doi":"10.1126/sciadv.abc6364","title":"The translocon-associated protein (TRAP) complex regulates quality control of N-linked glycosylation during ER stress","abstract":"Asparagine (N)-linked glycosylation is required for endoplasmic reticulum (ER) homeostasis, but how this co- and posttranslational modification is maintained during ER stress is unknown. Here, we introduce a fluorescence-based strategy to detect aberrant N-glycosylation in individual cells and identify a regulatory role for the heterotetrameric translocon-associated protein (TRAP) complex. Unexpectedly, cells with knockout of SSR3 or SSR4 subunits restore N-glycosylation over time concurrent with a diminished ER stress transcriptional signature. Activation of ER stress or silencing of the ER chaperone BiP exacerbates or rescues the glycosylation defects, respectively, indicating that SSR3 and SSR4 enable N-glycosylation during ER stress. Protein levels of the SSR3 subunit are ER stress and UBE2J1 dependent, revealing a mechanism that coordinates upstream N-glycosylation proficiency with downstream ER-associated degradation and proteostasis. The fidelity of N-glycosylation is not static in both nontransformed and tumor cells, and the TRAP complex regulates ER glycoprotein quality control under conditions of stress.","journal":"Science Advances","year":2021,"id":157108,"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":51,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9586,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":623099,"name":"Wei Cui","orcid":"0000-0001-8993-1503","position":1,"is_corresponding":false},{"id":623096,"name":"Thomas J. Hayman","orcid":"0000-0001-7046-2276","position":2,"is_corresponding":false},{"id":519253,"name":"Seok‐Ho Yu","orcid":"0000-0002-8372-1094","position":3,"is_corresponding":false},{"id":18590,"name":"Peng Zhao","orcid":"0000-0002-9296-5293","position":4,"is_corresponding":false},{"id":227815,"name":"Lance Wells","orcid":"0000-0003-4956-5363","position":5,"is_corresponding":false},{"id":390579,"name":"Richard Steet","orcid":"0000-0002-0975-4963","position":6,"is_corresponding":false},{"id":413470,"name":"Joseph N. Contessa","orcid":"0000-0001-9408-1865","position":7,"is_corresponding":false},{"id":281709,"name":"Chatchai Phoomak","orcid":"0000-0002-3808-8816","position":0,"is_corresponding":true}],"reference_count":40,"raw_metadata":null,"created_at":"2026-07-18T23:44:17.471040Z","pmid":"33523898","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":[]}