{"id":"5ab392b7-6448-5d01-9251-2bc7b1818f4a","stable_key":"2921131d-0ba0-51d3-8f59-8c4be3b9ac08:cucurbitacin-b-tnfr1","predicate":"reduces_tested_expression_of","statement":"Cucurbitacin B lowered TNF receptor 1 expression in human A549 cells without reducing the measured TRADD, RIPK1 and TRAF2 adaptor proteins.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"negative","is_public":true,"mechanism_event_id":"208557df-323b-53da-9d1e-a4f8fea28bea","mechanism_event_label":"The receptor changed before treating all downstream proteins as depleted.","subject":{"id":"a544a561-7647-55f6-8ba1-c7ab0133f968","slug":"cucurbitacin-b","display_name":"Cucurbitacin B","entity_type_key":"small_molecule"},"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":"208557df-323b-53da-9d1e-a4f8fea28bea","stable_key":"2921131d-0ba0-51d3-8f59-8c4be3b9ac08:cucurbitacin-b-tnfr1-event","event_type":"observed_relationship","label":"The receptor changed before treating all downstream proteins as depleted.","description":"Cucurbitacin B lowered TNF receptor 1 expression in human A549 cells without reducing the measured TRADD, RIPK1 and TRAF2 adaptor proteins.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"a544a561-7647-55f6-8ba1-c7ab0133f968","slug":"cucurbitacin-b","display_name":"Cucurbitacin B","entity_type_key":"small_molecule"},"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":""}]},"contexts":[{"dimension":"evidence_access","value_text":"Primary abstract","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"TNF-alpha-stimulated human A549 cells; dose/time not resolved in accessed abstract.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Protein abundance result, not demonstrated direct binding to TNFR1.","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":"The receptor changed before treating all downstream proteins as depleted.","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}],"evidence":[{"id":"8397bb49-c14b-581c-8f3f-f76b8bb5dc9e","evidence_kind":"source_excerpt","locator":"Lines 188-194","start_line":188,"end_line":194,"excerpt":"## cucurbitacin-b-tnfr1\nThe receptor changed before treating all downstream proteins as depleted.\nCucurbitacin B lowered TNF receptor 1 expression in human A549 cells without reducing the measured TRADD, RIPK1 and TRAF2 adaptor proteins.\nModel: TNF-alpha-stimulated human A549 cells; dose/time not resolved in accessed abstract.\nLimitations: Protein abundance result, not demonstrated direct binding to TNFR1.\nEvidence access: Primary abstract\nCucurbitacin 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","model_system":"TNF-alpha-stimulated human A549 cells; dose/time not resolved in accessed abstract.","directness":"reported_statement","verification_status":"source_derived_draft","notes":"Original curation paraphrase; evidence access and experimental limitations specified.","relationship":"supports","weight":1.0,"link_notes":"","source":{"id":"77324310-00ce-5d28-9fc7-595fddae86b9","stable_key":"import-2921131d-0ba0-51d3-8f59-8c4be3b9ac08","title":"Cucurbitacins: thiol chemistry, cytoskeleton, metabolic dependencies and signaling (2026-09-20)","document_type":"imported_text","citation_label":"AI-assisted research curation; primary references, access levels and experimental limitations individually identified. 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