{"id":"bf393f7c-d534-5828-8140-c53bd832ac2c","stable_key":"0a78b350-a082-585a-984b-3a9f329e1574:iscu-loss-chelator-atf4","predicate":"has_contextual_experimental_effect","statement":"ISCU depletion attenuated iron-chelation-induced ISR activation.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"negative","is_public":true,"mechanism_event_id":"9a4e3787-2f68-526e-a592-39be7a150cf3","mechanism_event_label":"iscu loss chelator atf4","subject":{"id":"49dfe714-0f9a-51b4-ba3b-a6886d3ce988","slug":"human-iscu-knockdown","display_name":"ISCU knockdown in human cells","entity_type_key":"protein_state"},"object":{"id":"1a9dd2b3-2552-5387-a086-66bea9f56058","slug":"atf4","display_name":"Human activating transcription factor 4 / ATF4","entity_type_key":"protein"},"evidence_count":1,"mechanism_event":{"id":"9a4e3787-2f68-526e-a592-39be7a150cf3","stable_key":"0a78b350-a082-585a-984b-3a9f329e1574:iscu-loss-chelator-atf4","event_type":"experimental_result","label":"iscu loss chelator atf4","description":"ISCU depletion attenuated iron-chelation-induced ISR activation.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"49dfe714-0f9a-51b4-ba3b-a6886d3ce988","slug":"human-iscu-knockdown","display_name":"ISCU knockdown in human cells","entity_type_key":"protein_state"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"1a9dd2b3-2552-5387-a086-66bea9f56058","slug":"atf4","display_name":"Human activating transcription factor 4 / ATF4","entity_type_key":"protein"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""}]},"contexts":[{"dimension":"access_level","value_text":"selected_indexed_full_text_passages","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"dose","value_text":"Unresolved; not inferred from another panel","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"duration","value_text":"72-hour siRNA reported; exact supplementary exposure schedule unresolved","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"endpoint","value_text":"ATF4/ISR immunoblot readout","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"evidence_cache","value_text":"artifacts/discovery-research/round2-sources/iscu-counterevidence-search.json; SHA256 91e6dd454b1fdecf0cf4d29d2579bf1eba148109e446059f91ea966f8bf0de21","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Human cultured cells; precise supplementary-panel cell assignment unresolved","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"Iron chelation; panel-specific agent and concentration unresolved","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Selected primary Results and figure legends accessed through indexed text. Supplements were not independently inspected. These results constrain a hypothesis; they do not test SLC25A39 loss or establish its bypass. Exact iron sensor and transporter substrate remain unresolved.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"organism","value_text":"Human","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_locator","value_text":"https://pmc.ncbi.nlm.nih.gov/articles/PMC10329284/ Results discussing Figure S6B/C","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"https://doi.org/10.1016/j.molcel.2023.05.031","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"85c45764-1d4a-5902-b773-f8cd95597f61","evidence_kind":"source_excerpt","locator":"Lines 48-59","start_line":48,"end_line":59,"excerpt":"ISCU depletion attenuated iron-chelation-induced ISR activation.\nprimary_references: https://doi.org/10.1016/j.molcel.2023.05.031\nprimary_locator: https://pmc.ncbi.nlm.nih.gov/articles/PMC10329284/ Results discussing Figure S6B/C\nevidence_cache: artifacts/discovery-research/round2-sources/iscu-counterevidence-search.json; SHA256 91e6dd454b1fdecf0cf4d29d2579bf1eba148109e446059f91ea966f8bf0de21\naccess_level: selected_indexed_full_text_passages\norganism: Human\nexperimental_model: Human cultured cells; precise supplementary-panel cell assignment unresolved\nduration: 72-hour siRNA reported; exact supplementary exposure schedule unresolved\nexposure: Iron chelation; panel-specific agent and concentration unresolved\ndose: Unresolved; not inferred from another panel\nendpoint: ATF4/ISR immunoblot readout\nlimitations: Selected primary Results and figure legends accessed through indexed text. Supplements were not independently inspected. These results constrain a hypothesis; they do not test SLC25A39 loss or establish its bypass. Exact iron sensor and transporter substrate remain unresolved.","model_system":"Human cultured cells; precise supplementary-panel cell assignment unresolved","directness":"reported_statement","verification_status":"source_derived_draft","notes":"Authored paraphrase with primary locator and unresolved conditions.","relationship":"supports","weight":1.0,"link_notes":"","source":{"id":"eeffd0c6-7b5e-5ec2-944b-6db3981fb281","stable_key":"import-0a78b350-a082-585a-984b-3a9f329e1574","title":"Requirements for iron-triggered DELE1 signaling","document_type":"imported_text","citation_label":"Primary study 10.1016/j.molcel.2023.05.031; targeted counterevidence curation, 2026-09-20.","file_path":"","sha256":"a51546326ca2ae4bbae2be44808672a526607fc7b68ade25f143a7a93cc08cf0","revision_id":"0d367584-8f47-5eda-946d-3d9f780b9b74","review_status":"unverified_draft","notes":""}}],"relations":[],"conflicts":[],"corrections":[],"research":null}