{"id":"6ae18437-7950-55e3-aa01-fe39246614df","stable_key":"aad5a443-96e9-52eb-963a-812e90f9f896:lycopene-nrf2-required","predicate":"abolished","statement":"Dominant-negative Nrf2 abolished the carotenoid-induced rise in phase II enzymes.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"context_dependent","is_public":true,"mechanism_event_id":"77e2ab3a-6d32-5b76-ae38-9d70200b3829","mechanism_event_label":"A signaling compound cannot produce this response when the experimental gene-control machinery is blocked.","subject":{"id":"b9330ea4-ab6d-56bb-9812-1293ccc193ca","slug":"dominant-negative-nrf2","display_name":"Study-specific dominant-negative human Nrf2 construct","entity_type_key":"protein_state"},"object":{"id":"f491d8a2-5670-5aef-a0a9-07a176b5957b","slug":"phase-ii-enzyme-induction","display_name":"Study-specific phase II enzyme induction","entity_type_key":"cellular_process"},"evidence_count":1,"mechanism_event":{"id":"77e2ab3a-6d32-5b76-ae38-9d70200b3829","stable_key":"aad5a443-96e9-52eb-963a-812e90f9f896:lycopene-nrf2-required-event","event_type":"biochemical_relationship","label":"A signaling compound cannot produce this response when the experimental gene-control machinery is blocked.","description":"Dominant-negative Nrf2 abolished the carotenoid-induced rise in phase II enzymes.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"dc472dd3-d383-567a-ab37-a9ec4e112df4","slug":"nfe2l2","display_name":"Human Nrf2 / NFE2L2","entity_type_key":"protein"},"role":"disabled_transcription_factor","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"0b16e027-7a68-55ae-8e33-eae8b5cd1e9e","slug":"lycopene","display_name":"Lycopene","entity_type_key":"small_molecule"},"role":"experimental_exposure","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"b9330ea4-ab6d-56bb-9812-1293ccc193ca","slug":"dominant-negative-nrf2","display_name":"Study-specific dominant-negative human Nrf2 construct","entity_type_key":"protein_state"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""},{"entity":{"id":"f491d8a2-5670-5aef-a0a9-07a176b5957b","slug":"phase-ii-enzyme-induction","display_name":"Study-specific phase II enzyme induction","entity_type_key":"cellular_process"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":3,"notes":""}]},"contexts":[{"dimension":"availability_state","value_text":"machinery_impairment","comparator":null,"unit":null,"notes":"Imported condition classification; unverified.","entity":null},{"dimension":"evidence_span","value_text":"{\"source_cache\": \"artifacts/lycopene-research/15657364.abstract.txt\", \"locator\": \"Primary indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"a25b93d6074a1e560bf1e163aa70c511e99199b9bb62ccdffdbe70e51fcc7c32\", \"start_char\": 0, \"end_char\": 1890, \"text_sha256\": \"a25b93d6074a1e560bf1e163aa70c511e99199b9bb62ccdffdbe70e51fcc7c32\"}","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Reporter, expression and dominant-negative transcription-factor experiments","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"Lycopene and ethanolic derivative extract","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Unidentified derivative extract was active; direct binding of intact lycopene to KEAP1 was not established.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"Lycopene research collection; topical membership is not evidence of a direct dietary effect.","comparator":null,"unit":null,"notes":"","entity":{"slug":"lycopene","display_name":"Lycopene","entity_type_key":"small_molecule"}},{"dimension":"organism","value_text":"Human cancer cell cultures","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"A signaling compound cannot produce this response when the experimental gene-control machinery is blocked.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[lycopene-p15657364] Carotenoids activate the antioxidant response element transcription system. (2005). https://pubmed.ncbi.nlm.nih.gov/15657364/ DOI: 10.1158/1535-7163.177.4.1","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue_or_cell_type","value_text":"ARE transcription and phase II enzyme expression","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"trigger_kind","value_text":"machinery_impairment","comparator":null,"unit":null,"notes":"Imported condition classification; unverified.","entity":null}],"evidence":[{"id":"f66177fc-65e0-51a1-a0dc-4f60626200a4","evidence_kind":"source_excerpt","locator":"Lines 481-492","start_line":481,"end_line":492,"excerpt":"### lycopene-nrf2-required\nDominant-negative Nrf2 abolished the carotenoid-induced rise in phase II enzymes.\nCondition category: machinery_impairment\nnutrient_topic: Lycopene research collection; topical membership is not evidence of a direct dietary effect.\nplain_language: A signaling compound cannot produce this response when the experimental gene-control machinery is blocked.\norganism: Human cancer cell cultures\ntissue_or_cell_type: ARE transcription and phase II enzyme expression\nexperimental_model: Reporter, expression and dominant-negative transcription-factor experiments\nlimitations: Unidentified derivative extract was active; direct binding of intact lycopene to KEAP1 was not established.\nexposure: Lycopene and ethanolic derivative extract\nevidence_span: {\"source_cache\": \"artifacts/lycopene-research/15657364.abstract.txt\", \"locator\": \"Primary indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"a25b93d6074a1e560bf1e163aa70c511e99199b9bb62ccdffdbe70e51fcc7c32\", \"start_char\": 0, \"end_char\": 1890, \"text_sha256\": \"a25b93d6074a1e560bf1e163aa70c511e99199b9bb62ccdffdbe70e51fcc7c32\"}\n[lycopene-p15657364] Carotenoids activate the antioxidant response element transcription system. 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