{"id":"6eb93bd8-eec7-5048-96bd-515fab92e7ed","stable_key":"74ef5bba-ee14-531c-b1bf-d1f297c56bb6:fisetin-atf4-basal-dependence","predicate":"silencing_reduces","statement":"ATF4 siRNA reduced the fisetin-associated basal glutathione increase; Nrf2 siRNA did not have the same basal requirement.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"context_dependent","is_public":true,"mechanism_event_id":"f30abd16-76bd-5bef-aaa2-f7f502ceacfd","mechanism_event_label":"Baseline glutathione regulation depended more on ATF4.","subject":{"id":"7a0fa32a-a00f-5500-bce7-8e8d101a8e2b","slug":"mouse-atf4","display_name":"Mouse activating transcription factor 4 / Atf4","entity_type_key":"protein"},"object":{"id":"0080449d-934e-51bf-b095-abff2ea065f3","slug":"mouse-fisetin-basal-gsh-response","display_name":"Mouse-cell basal glutathione response to fisetin","entity_type_key":"cellular_process"},"evidence_count":1,"mechanism_event":{"id":"f30abd16-76bd-5bef-aaa2-f7f502ceacfd","stable_key":"74ef5bba-ee14-531c-b1bf-d1f297c56bb6:fisetin-atf4-basal-dependence-event","event_type":"observed_relationship","label":"Baseline glutathione regulation depended more on ATF4.","description":"ATF4 siRNA reduced the fisetin-associated basal glutathione increase; Nrf2 siRNA did not have the same basal requirement.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"7a0fa32a-a00f-5500-bce7-8e8d101a8e2b","slug":"mouse-atf4","display_name":"Mouse activating transcription factor 4 / Atf4","entity_type_key":"protein"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"0080449d-934e-51bf-b095-abff2ea065f3","slug":"mouse-fisetin-basal-gsh-response","display_name":"Mouse-cell basal glutathione response to fisetin","entity_type_key":"cellular_process"},"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":""},{"entity":{"id":"95319607-3946-51b3-8235-400ec3223692","slug":"mouse-nfe2l2","display_name":"Mouse Nrf2 / Nfe2l2","entity_type_key":"protein"},"role":"context_participant","stoichiometry":null,"state_label":"","sequence_order":4,"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 transcription-factor silencing.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Baseline and oxidative-stress settings are distinct.","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":"Baseline glutathione regulation depended more on ATF4.","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":"ed9cbbb3-d8d8-54ff-ba29-7ba85d094bf3","evidence_kind":"source_excerpt","locator":"Lines 120-126","start_line":120,"end_line":126,"excerpt":"## fisetin-atf4-basal-dependence\nBaseline glutathione regulation depended more on ATF4.\nATF4 siRNA reduced the fisetin-associated basal glutathione increase; Nrf2 siRNA did not have the same basal requirement.\nModel: Mouse-cell transcription-factor silencing.\nLimitations: Baseline and oxidative-stress settings are distinct.\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 transcription-factor silencing.","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; primary references, access levels and experimental limitations individually identified. Not publisher full text.","file_path":"","sha256":"c30e0764cd34bd062cfcbfaf32357ef29dfda30e7d4153c545178140f5054e09","revision_id":"40ff52c0-f4b9-5820-8abb-ff002c6364a4","review_status":"unverified_draft","notes":""}}],"relations":[],"conflicts":[],"corrections":[],"research":null}