{"id":"5e6f5f2c-4cd5-5686-b9f6-933bcdb8385e","stable_key":"e13b03e1-a614-543a-ac1b-97df18cfe30d:iron-gpx4-ferroptosis","predicate":"regulates_susceptibility_to","statement":"GPX4 overexpression or knockdown altered lethality of all 12 tested ferroptosis inducers, but not 11 compounds with other lethal mechanisms.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"context_dependent","is_public":true,"mechanism_event_id":"690e677a-73fd-5159-8a2c-8b544d18ed71","mechanism_event_label":"The protective enzyme specifically controlled this iron-linked death pathway in the tested cells.","subject":{"id":"e9bb13ee-f238-51e6-9101-78ddfd11465c","slug":"gpx4","display_name":"GPX4","entity_type_key":"protein"},"object":{"id":"85ca0bb8-8a67-59fe-8334-e0f6617380b7","slug":"ferroptosis","display_name":"Ferroptosis","entity_type_key":"cellular_process"},"evidence_count":1,"mechanism_event":{"id":"690e677a-73fd-5159-8a2c-8b544d18ed71","stable_key":"e13b03e1-a614-543a-ac1b-97df18cfe30d:iron-gpx4-ferroptosis-event","event_type":"biochemical_relationship","label":"The protective enzyme specifically controlled this iron-linked death pathway in the tested cells.","description":"GPX4 overexpression or knockdown altered lethality of all 12 tested ferroptosis inducers, but not 11 compounds with other lethal mechanisms.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"e9bb13ee-f238-51e6-9101-78ddfd11465c","slug":"gpx4","display_name":"GPX4","entity_type_key":"protein"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"85ca0bb8-8a67-59fe-8334-e0f6617380b7","slug":"ferroptosis","display_name":"Ferroptosis","entity_type_key":"cellular_process"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""}]},"contexts":[{"dimension":"evidence_span","value_text":"{\"source_cache\": \"artifacts/iron-research/24439385.abstract.txt\", \"locator\": \"Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"f8d588af38ec5438fbec80971ead0764466237b3382492051aa3b3c297841703\", \"start_char\": 0, \"end_char\": 957, \"text_sha256\": \"f8d588af38ec5438fbec80971ead0764466237b3382492051aa3b3c297841703\"}","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Metabolomics, chemoproteomics, perturbation and cancer-cell sensitivity profiling","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"Two classes of ferroptosis-inducing compounds","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Preclinical drug-response mechanism; selenium or vitamin E supplementation is not established as a universal treatment.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"Iron research collection; topical membership is not evidence of a direct dietary effect.","comparator":null,"unit":null,"notes":"","entity":{"slug":"iron","display_name":"Iron","entity_type_key":"nutrient_element"}},{"dimension":"organism","value_text":"Human cancer-cell lines and mouse xenografts","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"The protective enzyme specifically controlled this iron-linked death pathway in the tested cells.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[iron-p24439385] Regulation of ferroptotic cancer cell death by GPX4. (2014). https://pubmed.ncbi.nlm.nih.gov/24439385/ DOI: 10.1016/j.cell.2013.12.010","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue_or_cell_type","value_text":"Glutathione/GPX4 antioxidant system","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"410f2934-5111-5d04-a3b1-aa959441c185","evidence_kind":"source_excerpt","locator":"Lines 1265-1276","start_line":1265,"end_line":1276,"excerpt":"### iron-gpx4-ferroptosis\nGPX4 overexpression or knockdown altered lethality of all 12 tested ferroptosis inducers, but not 11 compounds with other lethal mechanisms.\nCondition category: normal\nnutrient_topic: Iron research collection; topical membership is not evidence of a direct dietary effect.\nplain_language: The protective enzyme specifically controlled this iron-linked death pathway in the tested cells.\norganism: Human cancer-cell lines and mouse xenografts\ntissue_or_cell_type: Glutathione/GPX4 antioxidant system\nexperimental_model: Metabolomics, chemoproteomics, perturbation and cancer-cell sensitivity profiling\nlimitations: Preclinical drug-response mechanism; selenium or vitamin E supplementation is not established as a universal treatment.\nexposure: Two classes of ferroptosis-inducing compounds\nevidence_span: {\"source_cache\": \"artifacts/iron-research/24439385.abstract.txt\", \"locator\": \"Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"f8d588af38ec5438fbec80971ead0764466237b3382492051aa3b3c297841703\", \"start_char\": 0, \"end_char\": 957, \"text_sha256\": \"f8d588af38ec5438fbec80971ead0764466237b3382492051aa3b3c297841703\"}\n[iron-p24439385] Regulation of ferroptotic cancer cell death by GPX4. 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