{"id":"1a83c832-95e1-5d01-9566-86873677fd06","stable_key":"2921131d-0ba0-51d3-8f59-8c4be3b9ac08:cucurbitacin-b-adam17-gate","predicate":"when_inhibited_attenuates_loss_of","statement":"Adding a TNF-alpha-converting-enzyme inhibitor suppressed cucurbitacin B-associated TNFR1 down-regulation in human A549 cells.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"context_dependent","is_public":true,"mechanism_event_id":"915a7271-d581-596e-83b0-c46210e56401","mechanism_event_label":"A receptor-processing enzyme was implicated by an inhibitor experiment.","subject":{"id":"8d58be9b-98d0-5bc6-9c92-4c13adaba494","slug":"human-adam17","display_name":"Human ADAM metallopeptidase domain 17 / ADAM17","entity_type_key":"protein"},"object":{"id":"ecb44253-66b5-5fc5-b7ba-be2706be4b3b","slug":"human-tnfrsf1a","display_name":"Human TNF receptor 1 / TNFRSF1A","entity_type_key":"protein"},"evidence_count":1,"mechanism_event":{"id":"915a7271-d581-596e-83b0-c46210e56401","stable_key":"2921131d-0ba0-51d3-8f59-8c4be3b9ac08:cucurbitacin-b-adam17-gate-event","event_type":"observed_relationship","label":"A receptor-processing enzyme was implicated by an inhibitor experiment.","description":"Adding a TNF-alpha-converting-enzyme inhibitor suppressed cucurbitacin B-associated TNFR1 down-regulation in human A549 cells.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"8d58be9b-98d0-5bc6-9c92-4c13adaba494","slug":"human-adam17","display_name":"Human ADAM metallopeptidase domain 17 / ADAM17","entity_type_key":"protein"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"ecb44253-66b5-5fc5-b7ba-be2706be4b3b","slug":"human-tnfrsf1a","display_name":"Human TNF receptor 1 / TNFRSF1A","entity_type_key":"protein"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"a544a561-7647-55f6-8ba1-c7ab0133f968","slug":"cucurbitacin-b","display_name":"Cucurbitacin B","entity_type_key":"small_molecule"},"role":"context_participant","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""}]},"contexts":[{"dimension":"availability_state","value_text":"machinery_impairment","comparator":null,"unit":null,"notes":"Imported condition classification; unverified.","entity":null},{"dimension":"evidence_access","value_text":"Primary abstract","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Human A549 pharmacological perturbation.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Supports involvement of ADAM17-related processing; does not prove cucurbitacin binds or directly activates ADAM17.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"Cucurbitacins collection; species, compartment, exposure, co-substrates and manipulation remain explicit.","comparator":null,"unit":null,"notes":"","entity":{"slug":"cucurbitacin","display_name":"Cucurbitacins","entity_type_key":"chemical_species"}},{"dimension":"plain_language","value_text":"A receptor-processing enzyme was implicated by an inhibitor experiment.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"Cucurbitacin B Down-Regulates TNF Receptor 1 Expression and Inhibits the TNF-α-Dependent Nuclear Factor κB Signaling Pathway in Human Lung Adenocarcinoma A549 Cells. · 2022 · https://pubmed.ncbi.nlm.nih.gov/35806134/ · DOI 10.3390/ijms23137130","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"trigger_kind","value_text":"machinery_impairment","comparator":null,"unit":null,"notes":"Imported condition classification; 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