{"id":"d1bcb5f8-479b-564f-b8cc-79ee2150c1e0","stable_key":"d71929ae-ed38-52ed-b512-f92b9b148b71:apt2-rescue-s122a-protein","predicate":"has_contextual_experimental_result","statement":"S122A APT2 re-expression did not reproduce the wild-type reduction in GPX4 protein in APT2-depleted A375 cells.","claim_class":"observational","status":"source_derived_draft","evidence_grade":"ungraded","direction":"neutral","is_public":true,"mechanism_event_id":"81713b12-7694-52f3-bac2-08f212ec9564","mechanism_event_label":"apt2-rescue-s122a-protein","subject":{"id":"c923235b-b718-5d0f-880e-6bb908d8b3c5","slug":"human-apt2-s122a-rescue-a375","display_name":"Human A375 APT2 knockdown with HA-APT2 S122A re-expression","entity_type_key":"protein_state"},"object":{"id":"3a44f7ad-80d1-51ff-ba8b-3f92e2f38773","slug":"human-gpx4-protein-abundance","display_name":"GPX4 protein abundance in human cells","entity_type_key":"cellular_process"},"evidence_count":1,"mechanism_event":{"id":"81713b12-7694-52f3-bac2-08f212ec9564","stable_key":"d71929ae-ed38-52ed-b512-f92b9b148b71:apt2-rescue-s122a-protein","event_type":"experimental_result","label":"apt2-rescue-s122a-protein","description":"S122A APT2 re-expression did not reproduce the wild-type reduction in GPX4 protein in APT2-depleted A375 cells.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"c923235b-b718-5d0f-880e-6bb908d8b3c5","slug":"human-apt2-s122a-rescue-a375","display_name":"Human A375 APT2 knockdown with HA-APT2 S122A re-expression","entity_type_key":"protein_state"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"3a44f7ad-80d1-51ff-ba8b-3f92e2f38773","slug":"human-gpx4-protein-abundance","display_name":"GPX4 protein abundance in human cells","entity_type_key":"cellular_process"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"f2ffef5b-5457-50a8-b787-b8f24430f610","slug":"lypla2","display_name":"LYPLA2","entity_type_key":"protein"},"role":"re-expressed protein","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""},{"entity":{"id":"e9bb13ee-f238-51e6-9101-78ddfd11465c","slug":"gpx4","display_name":"GPX4","entity_type_key":"protein"},"role":"measured protein","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":"experimental_model","value_text":"Human A375 melanoma cells with APT2 shRNA and lentiviral rescue constructs","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"HA-tagged rescue constructs; Figure 6j: 48-hour RSL3 challenge, n=3 independent experiments. Exact RSL3 concentrations follow the figure dose response and are not inferred here.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"C2S affects APT2 palmitoylation/localization and is not identical to the S122A catalytic-site perturbation. Null comparisons do not prove equivalence. No sulforaphane or solasonine tested in this rescue experiment.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"organism","value_text":"Human","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_locator","value_text":"Figure 6i-j; Results: Inhibition of APT2 suppresses ferroptosis.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"https://doi.org/10.1038/s41467-025-56344-5","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":"2b3ee055-c9f9-595f-9ca0-25cd8d38e3bb","evidence_kind":"source_excerpt","locator":"Lines 42-48","start_line":42,"end_line":48,"excerpt":"S122A APT2 re-expression did not reproduce the wild-type reduction in GPX4 protein in APT2-depleted A375 cells.\nprimary_references: https://doi.org/10.1038/s41467-025-56344-5\nprimary_locator: Figure 6i-j; Results: Inhibition of APT2 suppresses ferroptosis.\norganism: Human\nexperimental_model: Human A375 melanoma cells with APT2 shRNA and lentiviral rescue constructs\nexposure: HA-tagged rescue constructs; Figure 6j: 48-hour RSL3 challenge, n=3 independent experiments. Exact RSL3 concentrations follow the figure dose response and are not inferred here.\nlimitations: C2S affects APT2 palmitoylation/localization and is not identical to the S122A catalytic-site perturbation. Null comparisons do not prove equivalence. No sulforaphane or solasonine tested in this rescue experiment.","model_system":"Human A375 melanoma cells with APT2 shRNA and lentiviral rescue constructs","directness":"reported_statement","verification_status":"source_derived_draft","notes":"Curator paraphrase, not a publisher quotation. Methodological inference is explicitly identified.","relationship":"supports","weight":1.0,"link_notes":"","source":{"id":"15a55d0b-bd44-54e4-9080-5526d1a9744d","stable_key":"import-d71929ae-ed38-52ed-b512-f92b9b148b71","title":"APT2, STAT3 and GPX4: opposing branches and assay qualification","document_type":"imported_text","citation_label":"Primary observations: 10.1038/s41467-025-56344-5 and 10.1002/ptr.70245; selected full-text review 2026-09-20.","file_path":"","sha256":"6fd94803c436074e7b2c15e9a817e751c3d95f6fe1d35a4af63ab641a8f33fe0","revision_id":"d59d5472-18d2-5feb-bc2e-529ceda00956","review_status":"unverified_draft","notes":""}}],"relations":[],"conflicts":[],"corrections":[],"research":null}