{"id":"0dbee5be-ae69-50fa-a6b0-ff0ac24578a1","stable_key":"research:lrp8-loss-promotes-gpx4-stalling","predicate":"loss-increases","statement":"LRP8 loss caused GPX4 UGA-associated ribosome stalling in the tested cancer cells.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"literature_reviewed:direct_experimental","direction":"positive","is_public":true,"mechanism_event_id":"c10fd2cd-9296-578f-ba23-48dee8f70e09","mechanism_event_label":"Disrupted selenium uptake hindered GPX4 production in these cancer cells.","subject":{"id":"f47ee853-9252-56f4-8e2a-48ede17ed3a3","slug":"lrp8","display_name":"ApoER2 / LRP8","entity_type_key":"protein"},"object":{"id":"a7b7632a-44fd-557d-9f8c-56e30d908abb","slug":"gpx4-uga-ribosome-stalling","display_name":"Ribosome stalling at GPX4 UGA","entity_type_key":"cellular_process"},"evidence_count":1,"mechanism_event":{"id":"c10fd2cd-9296-578f-ba23-48dee8f70e09","stable_key":"research:lrp8-loss-promotes-gpx4-stalling","event_type":"genetic-perturbation","label":"Disrupted selenium uptake hindered GPX4 production in these cancer cells.","description":"LRP8 loss caused GPX4 UGA-associated ribosome stalling in the tested cancer cells.","status":"active","compartment":{"slug":"cytosol","display_name":"Cytosol"},"participants":[{"entity":{"id":"f47ee853-9252-56f4-8e2a-48ede17ed3a3","slug":"lrp8","display_name":"ApoER2 / LRP8","entity_type_key":"protein"},"role":"perturbed-protein","stoichiometry":null,"state_label":"deleted","sequence_order":0,"notes":""},{"entity":{"id":"e9bb13ee-f238-51e6-9101-78ddfd11465c","slug":"gpx4","display_name":"GPX4","entity_type_key":"protein"},"role":"translation-product","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"a7b7632a-44fd-557d-9f8c-56e30d908abb","slug":"gpx4-uga-ribosome-stalling","display_name":"Ribosome stalling at GPX4 UGA","entity_type_key":"cellular_process"},"role":"measured-event","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""},{"entity":{"id":"dc89d7e2-8f89-577b-838f-42bf5d8ec7c8","slug":"selenium","display_name":"Selenium","entity_type_key":"nutrient_element"},"role":"limiting-cellular-supply","stoichiometry":null,"state_label":"","sequence_order":3,"notes":""}]},"contexts":[{"dimension":"cell_type","value_text":"cancer cell lines","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Genetic disruption and ribosome analyses","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Tumor-cell result; GPX4 priority is context dependent.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"organism","value_text":"human","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"58547440-8246-55cc-9a36-95351a608dd4","evidence_kind":"curated_literature_summary","locator":"lines 594-604","start_line":594,"end_line":604,"excerpt":"## lrp8-loss-promotes-gpx4-stalling\n\nDisrupted selenium uptake hindered GPX4 production in these cancer cells.\n\nLRP8 loss caused GPX4 UGA-associated ribosome stalling in the tested cancer cells.\n\nOrganism: human\nCell type: cancer cell lines\nExperimental model: Genetic disruption and ribosome analyses\nLimitations: Tumor-cell result; GPX4 priority is context dependent.\nPrimary reference: [Ribosome stalling during selenoprotein translation exposes a ferroptosis vulnerability](https://pubmed.ncbi.nlm.nih.gov/35637349/)","model_system":"Genetic disruption and ribosome analyses","directness":"author_interpretation","verification_status":"secondary_verified","notes":"Curated summary; inspect the linked primary papers for original methods and results.","relationship":"supports","weight":1.0,"link_notes":"","source":{"id":"4f892f13-06ea-5199-a33c-a703f35c80ae","stable_key":"selenium-research-2026-09-17","title":"Selenium: literature corrections and mechanism additions","document_type":"curated_literature_review","citation_label":"Metabolic Ledger literature curation, 17 September 2026; primary papers linked individually","file_path":"","sha256":"0b818b10c1c7120e5caf7f4d4019d7bd025d745692e424f515d3ef903c9ab7f3","revision_id":"80984e03-5f0f-5877-8094-afef7637444e","review_status":"secondary_verified","notes":"Secondary curated summaries of primary experiments, with explicit models and limitations. Not archived primary full text."}}],"relations":[],"conflicts":[],"corrections":[],"research":{"topic":"selenoprotein-translation","plain_language":"Disrupted selenium uptake hindered GPX4 production in these cancer cells.","evidence_scope":"direct_experimental","papers":[{"key":"li-2022-gpx4-stalling","title":"Ribosome stalling during selenoprotein translation exposes a ferroptosis vulnerability","url":"https://pubmed.ncbi.nlm.nih.gov/35637349/","doi":"10.1038/s41589-022-01033-3","year":2022,"model":"Human cancer-cell genetic screens and ribosome analyses","summary":"Links LRP8 loss to impaired GPX4 synthesis through UGA-associated ribosome stalling."}]}}