{"id":"6b93cfa0-b107-5f3a-ae53-58d4fb538744","stable_key":"88eb7407-f147-558b-889b-0c89c4e0aa4a:spermidine-proteasome","predicate":"with_erastin_reduces","statement":"Spermidine/erastin treatment reduced proteasome activity and NRF2 degradation in the reported prostate-cell experiments.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"context_dependent","is_public":true,"mechanism_event_id":"cfda2b37-911c-55f6-9c5e-fc2fd7edfd87","mechanism_event_label":"Protein accumulation can involve slower removal as well as faster production.","subject":{"id":"7014993c-468f-5c6b-ab04-80c87f9dfd9f","slug":"spermidine","display_name":"Spermidine","entity_type_key":"small_molecule"},"object":{"id":"e03951ad-3213-5c75-aada-f463fe6e0caf","slug":"human-prostate-cell-proteasome-activity","display_name":"Human prostate-cell proteasome activity","entity_type_key":"cellular_process"},"evidence_count":1,"mechanism_event":{"id":"cfda2b37-911c-55f6-9c5e-fc2fd7edfd87","stable_key":"88eb7407-f147-558b-889b-0c89c4e0aa4a:spermidine-proteasome-event","event_type":"observed_relationship","label":"Protein accumulation can involve slower removal as well as faster production.","description":"Spermidine/erastin treatment reduced proteasome activity and NRF2 degradation in the reported prostate-cell experiments.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"7014993c-468f-5c6b-ab04-80c87f9dfd9f","slug":"spermidine","display_name":"Spermidine","entity_type_key":"small_molecule"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"e03951ad-3213-5c75-aada-f463fe6e0caf","slug":"human-prostate-cell-proteasome-activity","display_name":"Human prostate-cell proteasome activity","entity_type_key":"cellular_process"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"b5dcb638-5d9d-5506-b6e4-f35a6676eb78","slug":"erastin","display_name":"Erastin","entity_type_key":"small_molecule"},"role":"context_participant","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""},{"entity":{"id":"dc472dd3-d383-567a-ab37-a9ec4e112df4","slug":"nfe2l2","display_name":"Human Nrf2 / NFE2L2","entity_type_key":"protein"},"role":"context_participant","stoichiometry":null,"state_label":"","sequence_order":3,"notes":""}]},"contexts":[{"dimension":"evidence_access","value_text":"Primary full text","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Human-cell proteasome activity and protein-stability assays.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Not proof that spermidine directly binds a specific proteasome subunit.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"Spermidine collection; molecular form, preparation, species, exposure and manipulation remain explicit.","comparator":null,"unit":null,"notes":"","entity":{"slug":"spermidine","display_name":"Spermidine","entity_type_key":"small_molecule"}},{"dimension":"plain_language","value_text":"Protein accumulation can involve slower removal as well as faster production.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"Spermidine inactivates proteasome activity and enhances ferroptosis in prostate cancer. · 2025 · https://pubmed.ncbi.nlm.nih.gov/40486852/ · DOI 10.1016/j.apsb.2025.02.023","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"80f8b953-5795-539b-8959-40ffce3cbef4","evidence_kind":"source_excerpt","locator":"Lines 518-524","start_line":518,"end_line":524,"excerpt":"## spermidine-proteasome\nProtein accumulation can involve slower removal as well as faster production.\nSpermidine/erastin treatment reduced proteasome activity and NRF2 degradation in the reported prostate-cell experiments.\nModel: Human-cell proteasome activity and protein-stability assays.\nLimitations: Not proof that spermidine directly binds a specific proteasome subunit.\nEvidence access: Primary full text\nSpermidine inactivates proteasome activity and enhances ferroptosis in prostate cancer. · 2025 · https://pubmed.ncbi.nlm.nih.gov/40486852/ · DOI 10.1016/j.apsb.2025.02.023","model_system":"Human-cell proteasome activity and protein-stability assays.","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":"4348f3f8-0180-58a3-b61c-55d03bb322d2","stable_key":"import-88eb7407-f147-558b-889b-0c89c4e0aa4a","title":"Spermidine: biosynthesis, hypusination, transport 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":"8eec8784bc2bd0384cfd53c6603c4ced8e53c227d9ab29ed85594c43e34c68ef","revision_id":"7c421a18-4526-59f6-b84e-4be533bc35ac","review_status":"unverified_draft","notes":""}}],"relations":[],"conflicts":[],"corrections":[],"research":null}