{"id":"76c59ff2-5ef9-5401-b679-6cdd762da300","stable_key":"a2968a2f-5b00-5212-8b8c-8a4262bcb149:ascorbate-restoration-depends-on-mutation-and-acetylation","predicate":"context_dependently_restores","statement":"The ability of ascorbic acid to restore TET2 activity in cells depended on N-terminal and C-terminal lysine acetylation and on the nature of the TET2 mutation.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"context_dependent","is_public":true,"mechanism_event_id":"9d66e1ac-e324-576e-9bce-158d64195545","mechanism_event_label":"The ability of ascorbic acid to restore TET2 activity in cells depended on N-terminal and C-terminal lysine acetylation and on the nature of the TET2 mutation.","subject":{"id":"38d0c4d9-53d1-5239-bfe3-c1b5e9b79085","slug":"ascorbate","display_name":"L-Ascorbate","entity_type_key":"small_molecule"},"object":{"id":"5433ea92-f679-5b25-a872-cb8a636ae4e1","slug":"tet2-human","display_name":"Human TET2","entity_type_key":"protein"},"evidence_count":1,"mechanism_event":{"id":"9d66e1ac-e324-576e-9bce-158d64195545","stable_key":"a2968a2f-5b00-5212-8b8c-8a4262bcb149:ascorbate-restoration-depends-on-mutation-and-acetylation-event","event_type":"observed_relationship","label":"The ability of ascorbic acid to restore TET2 activity in cells depended on N-terminal and C-terminal lysine acetylation and on the nature of the TET2 mutation.","description":"Whether vitamin C can revive the enzyme depends on which mutation the patient has.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"38d0c4d9-53d1-5239-bfe3-c1b5e9b79085","slug":"ascorbate","display_name":"L-Ascorbate","entity_type_key":"small_molecule"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"5433ea92-f679-5b25-a872-cb8a636ae4e1","slug":"tet2-human","display_name":"Human TET2","entity_type_key":"protein"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""}]},"contexts":[{"dimension":"availability_state","value_text":"machinery_impairment","comparator":null,"unit":null,"notes":"Imported condition classification; unverified.","entity":null},{"dimension":"duration","value_text":"Culture experiments","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"TET2-mutant myeloid neoplasia cell systems with acetyltransferase and deacetylase modulation","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"Ascorbic acid, with pharmacological modulation of acetyltransferases and histone deacetylases","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Which mutations respond is not resolved here; the study proposes combinations rather than demonstrating clinical benefit.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"organism","value_text":"Homo sapiens","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"Whether vitamin C can revive the enzyme depends on which mutation the patient has.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[mustafi-2020] Context dependent effects of ascorbic acid treatment in TET2 mutant myeloid neoplasia (2020). https://pubmed.ncbi.nlm.nih.gov/32895473/ DOI: 10.1038/s42003-020-01220-9","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue","value_text":"Myeloid neoplasia cells","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":"64c4c832-6100-5b0d-945f-f0ba0f7df3c3","evidence_kind":"source_excerpt","locator":"Lines 173-181","start_line":173,"end_line":181,"excerpt":"## ascorbate-restoration-depends-on-mutation-and-acetylation\nThe ability of ascorbic acid to restore TET2 activity in cells depended on N-terminal and C-terminal lysine acetylation and on the nature of the TET2 mutation.\nModel/species: TET2-mutant myeloid neoplasia cell systems with acetyltransferase and deacetylase modulation\nOrganism: Homo sapiens\nTissue/system: Myeloid neoplasia cells\nExposure: Ascorbic acid, with pharmacological modulation of acetyltransferases and histone deacetylases\nDuration: Culture experiments\nLimits: Which mutations respond is not resolved here; the study proposes combinations rather than demonstrating clinical benefit.\nPrimary reference: [mustafi-2020] Context dependent effects of ascorbic acid treatment in TET2 mutant myeloid neoplasia (2020). https://pubmed.ncbi.nlm.nih.gov/32895473/ DOI: 10.1038/s42003-020-01220-9","model_system":"TET2-mutant myeloid neoplasia cell systems with acetyltransferase and deacetylase modulation","directness":"reported_statement","verification_status":"source_derived_draft","notes":"","relationship":"supports","weight":1.0,"link_notes":"","source":{"id":"c0b9b176-985b-55c7-b8f5-f3ca16a7ddfe","stable_key":"import-a2968a2f-5b00-5212-8b8c-8a4262bcb149","title":"TET2 loss and malignancy: the step between a nutrient-responsive enzyme and the disease (2026-09-23)","document_type":"imported_text","citation_label":"Original AI-assisted curation of twelve primary studies located by Europe PMC title search, with every statement drafted from the retrieved abstract. Two pairs share a laboratory and are recorded as one line of evidence each. Genetic loss of function, pharmacological exposure and dietary depletion are kept as separate record types. Not publisher full text.","file_path":"","sha256":"22e2c8388d4f0c1813546ba6a9ccee3fa14c0c8f578bd9bd80103c1390b2536b","revision_id":"fbc29d8d-0420-562c-bfdb-1b5af42f2d08","review_status":"unverified_draft","notes":""}}],"relations":[],"conflicts":[],"corrections":[],"research":null}