{"id":"69cfbebb-2098-5fab-9be9-b818c88419be","stable_key":"74ef5bba-ee14-531c-b1bf-d1f297c56bb6:fisetin-stress-cooperation","predicate":"cooperates_with","statement":"Under oxidative stress, siRNA experiments implicated both Nrf2 and ATF4 in the mouse-cell glutathione response to fisetin.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"context_dependent","is_public":true,"mechanism_event_id":"2561cca8-8293-5554-a10c-f5a30a726a7e","mechanism_event_label":"The cell relies on both regulators during stress.","subject":{"id":"95319607-3946-51b3-8235-400ec3223692","slug":"mouse-nfe2l2","display_name":"Mouse Nrf2 / Nfe2l2","entity_type_key":"protein"},"object":{"id":"7a0fa32a-a00f-5500-bce7-8e8d101a8e2b","slug":"mouse-atf4","display_name":"Mouse activating transcription factor 4 / Atf4","entity_type_key":"protein"},"evidence_count":1,"mechanism_event":{"id":"2561cca8-8293-5554-a10c-f5a30a726a7e","stable_key":"74ef5bba-ee14-531c-b1bf-d1f297c56bb6:fisetin-stress-cooperation-event","event_type":"observed_relationship","label":"The cell relies on both regulators during stress.","description":"Under oxidative stress, siRNA experiments implicated both Nrf2 and ATF4 in the mouse-cell glutathione response to fisetin.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"95319607-3946-51b3-8235-400ec3223692","slug":"mouse-nfe2l2","display_name":"Mouse Nrf2 / Nfe2l2","entity_type_key":"protein"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"7a0fa32a-a00f-5500-bce7-8e8d101a8e2b","slug":"mouse-atf4","display_name":"Mouse activating transcription factor 4 / Atf4","entity_type_key":"protein"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"dee05061-c3f3-5226-8054-dd58b76a585d","slug":"fisetin","display_name":"Fisetin","entity_type_key":"small_molecule"},"role":"context_participant","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""},{"entity":{"id":"b44c9e27-4bbb-52d3-a022-14cddded5073","slug":"glutathione","display_name":"GSH","entity_type_key":"small_molecule"},"role":"context_participant","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_access","value_text":"Primary abstract","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Mouse-cell gene-silencing comparisons.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Cooperation in this assay is not proof of universal transcriptional synergy.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"Fisetin collection; molecular form, preparation, species, exposure and manipulation remain explicit.","comparator":null,"unit":null,"notes":"","entity":{"slug":"fisetin","display_name":"Fisetin","entity_type_key":"small_molecule"}},{"dimension":"plain_language","value_text":"The cell relies on both regulators during stress.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"Concurrent regulation of the transcription factors Nrf2 and ATF4 mediates the enhancement of glutathione levels by the flavonoid fisetin. · 2013 · https://pubmed.ncbi.nlm.nih.gov/23618921/ · DOI 10.1016/j.bcp.2013.04.010","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":"727d79ce-45cf-5724-a0f4-b8096dfe9821","evidence_kind":"source_excerpt","locator":"Lines 128-134","start_line":128,"end_line":134,"excerpt":"## fisetin-stress-cooperation\nThe cell relies on both regulators during stress.\nUnder oxidative stress, siRNA experiments implicated both Nrf2 and ATF4 in the mouse-cell glutathione response to fisetin.\nModel: Mouse-cell gene-silencing comparisons.\nLimitations: Cooperation in this assay is not proof of universal transcriptional synergy.\nEvidence access: Primary abstract\nConcurrent regulation of the transcription factors Nrf2 and ATF4 mediates the enhancement of glutathione levels by the flavonoid fisetin. · 2013 · https://pubmed.ncbi.nlm.nih.gov/23618921/ · DOI 10.1016/j.bcp.2013.04.010","model_system":"Mouse-cell gene-silencing comparisons.","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":"1108bfff-6504-5152-a51f-ff3d7c27c282","stable_key":"import-74ef5bba-ee14-531c-b1bf-d1f297c56bb6","title":"Fisetin: metabolism, cell-state responses and cross-nutrient mechanisms (2026-09-19)","document_type":"imported_text","citation_label":"AI-assisted research curation; 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