{"id":"9ed8736b-5969-5a93-bf9b-220e04ec5363","stable_key":"0ad8610d-d575-5870-b7cd-763a9f750783:copper-cu-mek1-signaling","predicate":"copper_binding_supports","statement":"MEK1 mutations disrupting copper binding reduced BRAF V600E-driven signaling in the tested human and mouse systems.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"context_dependent","is_public":true,"mechanism_event_id":"511cd4a7-4e7d-5afc-abf5-8f82109d5806","mechanism_event_label":"Copper binding influenced an enzyme in a growth-signaling chain.","subject":{"id":"bc047045-23f3-5783-9209-6a834bad4ecb","slug":"map2k1","display_name":"Human mitogen-activated protein kinase kinase 1 / MEK1 / MAP2K1","entity_type_key":"protein"},"object":{"id":"10fa4fa0-4b4a-58f0-b45e-825220ffeb2c","slug":"mapk-pathway-signaling","display_name":"MEK-ERK MAPK pathway signaling","entity_type_key":"cellular_process"},"evidence_count":1,"mechanism_event":{"id":"511cd4a7-4e7d-5afc-abf5-8f82109d5806","stable_key":"0ad8610d-d575-5870-b7cd-763a9f750783:copper-cu-mek1-signaling-event","event_type":"biochemical_relationship","label":"Copper binding influenced an enzyme in a growth-signaling chain.","description":"MEK1 mutations disrupting copper binding reduced BRAF V600E-driven signaling in the tested human and mouse systems.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"9f0afdde-1ec1-5c8a-bb5e-f3b2b75f67f6","slug":"copper","display_name":"Copper","entity_type_key":"nutrient_element"},"role":"bound regulatory metal","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"bc047045-23f3-5783-9209-6a834bad4ecb","slug":"map2k1","display_name":"Human mitogen-activated protein kinase kinase 1 / MEK1 / MAP2K1","entity_type_key":"protein"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"10fa4fa0-4b4a-58f0-b45e-825220ffeb2c","slug":"mapk-pathway-signaling","display_name":"MEK-ERK MAPK pathway signaling","entity_type_key":"cellular_process"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""}]},"contexts":[{"dimension":"evidence_span","value_text":"{\"source_cache\": \"artifacts/copper-research/24717435.abstract.txt\", \"locator\": \"Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"4eee319f693bd307d3930073167395e5ef454f07d976ca834539b637ec4406ef\", \"start_char\": 0, \"end_char\": 1471, \"text_sha256\": \"4eee319f693bd307d3930073167395e5ef454f07d976ca834539b637ec4406ef\"}","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Copper-binding MEK1 mutants, CTR1 perturbation and tumor models","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"CTR1 reduction, MEK1 copper-binding disruption and chelation","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Preclinical mechanism; does not establish dietary copper as a cancer cause or copper restriction as a treatment.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"Copper research collection; topical membership is not evidence of a direct dietary effect.","comparator":null,"unit":null,"notes":"","entity":{"slug":"copper","display_name":"Copper","entity_type_key":"nutrient_element"}},{"dimension":"organism","value_text":"Human and mouse experimental systems","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"Copper binding influenced an enzyme in a growth-signaling chain.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[copper-p24717435] Copper is required for oncogenic BRAF signalling and tumorigenesis. (2014). https://pubmed.ncbi.nlm.nih.gov/24717435/ DOI: 10.1038/nature13180","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue_or_cell_type","value_text":"BRAF V600E-driven signaling and tumor models","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"ba378287-8935-5ffe-928f-d417b33e6a03","evidence_kind":"source_excerpt","locator":"Lines 1222-1233","start_line":1222,"end_line":1233,"excerpt":"### copper-cu-mek1-signaling\nMEK1 mutations disrupting copper binding reduced BRAF V600E-driven signaling in the tested human and mouse systems.\nCondition category: normal\nnutrient_topic: Copper research collection; topical membership is not evidence of a direct dietary effect.\nplain_language: Copper binding influenced an enzyme in a growth-signaling chain.\norganism: Human and mouse experimental systems\ntissue_or_cell_type: BRAF V600E-driven signaling and tumor models\nexperimental_model: Copper-binding MEK1 mutants, CTR1 perturbation and tumor models\nlimitations: Preclinical mechanism; does not establish dietary copper as a cancer cause or copper restriction as a treatment.\nexposure: CTR1 reduction, MEK1 copper-binding disruption and chelation\nevidence_span: {\"source_cache\": \"artifacts/copper-research/24717435.abstract.txt\", \"locator\": \"Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"4eee319f693bd307d3930073167395e5ef454f07d976ca834539b637ec4406ef\", \"start_char\": 0, \"end_char\": 1471, \"text_sha256\": \"4eee319f693bd307d3930073167395e5ef454f07d976ca834539b637ec4406ef\"}\n[copper-p24717435] Copper is required for oncogenic BRAF signalling and tumorigenesis. 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