{"id":"4d22e19a-30f5-5472-ba17-b3d1bb8fed04","stable_key":"a2968a2f-5b00-5212-8b8c-8a4262bcb149:vitamin-c-cannot-replace-lost-tet2","predicate":"loss_reduces","statement":"TET2 knockout in human HAP1 cells lowered 5-hydroxymethylcytosine and 5-formylcytosine measured by 2D-UPLC-MS/MS, and vitamin C treatment did not restore them to the levels seen in treated wild-type cells, so loss of one TET paralog was not compensated by the remaining ones.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"negative","is_public":true,"mechanism_event_id":"aa221d2d-641e-509e-9f71-73e8c42fc290","mechanism_event_label":"TET2 knockout in human HAP1 cells lowered 5-hydroxymethylcytosine and 5-formylcytosine measured by 2D-UPLC-MS/MS, and vitamin C treatment did not restore them to the levels seen in treated wild-type cells, so loss of one TET paralog was not compensated by the remaining ones.","subject":{"id":"5433ea92-f679-5b25-a872-cb8a636ae4e1","slug":"tet2-human","display_name":"Human TET2","entity_type_key":"protein"},"object":{"id":"5b1cc801-596e-5763-976c-4ea4979054ff","slug":"human-hap1-tet2-oxidation-products","display_name":"Cytosine oxidation products in human HAP1 TET-knockout cells","entity_type_key":"cellular_process"},"evidence_count":1,"mechanism_event":{"id":"aa221d2d-641e-509e-9f71-73e8c42fc290","stable_key":"a2968a2f-5b00-5212-8b8c-8a4262bcb149:vitamin-c-cannot-replace-lost-tet2-event","event_type":"observed_relationship","label":"TET2 knockout in human HAP1 cells lowered 5-hydroxymethylcytosine and 5-formylcytosine measured by 2D-UPLC-MS/MS, and vitamin C treatment did not restore them to the levels seen in treated wild-type cells, so loss of one TET paralog was not compensated by the remaining ones.","description":"Vitamin C cannot fully substitute for a TET2 that is missing.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"5433ea92-f679-5b25-a872-cb8a636ae4e1","slug":"tet2-human","display_name":"Human TET2","entity_type_key":"protein"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"5b1cc801-596e-5763-976c-4ea4979054ff","slug":"human-hap1-tet2-oxidation-products","display_name":"Cytosine oxidation products in human HAP1 TET-knockout cells","entity_type_key":"cellular_process"},"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":"Human HAP1 cells with single and double TET knockouts","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"Vitamin C treatment of wild-type and TET-knockout cells","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"A near-haploid cell line, not a haematopoietic cell; a knockout is not a patient's point mutation.","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":"Vitamin C cannot fully substitute for a TET2 that is missing.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[kusmierek-2025] Loss of TET2 activity limits the ability of vitamin C to activate DNA demethylation in human HAP1 cells (2025). https://pubmed.ncbi.nlm.nih.gov/41287077/ DOI: 10.1186/s13072-025-00634-1","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue","value_text":"HAP1 cell line","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":"4d107d78-f7d9-5ddb-8ffa-2b8368c7c3c2","evidence_kind":"source_excerpt","locator":"Lines 183-191","start_line":183,"end_line":191,"excerpt":"## vitamin-c-cannot-replace-lost-tet2\nTET2 knockout in human HAP1 cells lowered 5-hydroxymethylcytosine and 5-formylcytosine measured by 2D-UPLC-MS/MS, and vitamin C treatment did not restore them to the levels seen in treated wild-type cells, so loss of one TET paralog was not compensated by the remaining ones.\nModel/species: Human HAP1 cells with single and double TET knockouts\nOrganism: Homo sapiens\nTissue/system: HAP1 cell line\nExposure: Vitamin C treatment of wild-type and TET-knockout cells\nDuration: Culture experiments\nLimits: A near-haploid cell line, not a haematopoietic cell; a knockout is not a patient's point mutation.\nPrimary reference: [kusmierek-2025] Loss of TET2 activity limits the ability of vitamin C to activate DNA demethylation in human HAP1 cells (2025). https://pubmed.ncbi.nlm.nih.gov/41287077/ DOI: 10.1186/s13072-025-00634-1","model_system":"Human HAP1 cells with single and double TET knockouts","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}