{"id":"ad8f45c5-ad48-58a3-9f70-7b17a4a20096","stable_key":"4d8e4781-3878-5818-8d0a-7dbd6e024555:chromium-chromate-chk2","predicate":"induces_phosphorylation_of","statement":"Chromate exposure induced CHK2 phosphorylation as part of the ATM response in standard ascorbate-poor human cell cultures.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"context_dependent","is_public":true,"mechanism_event_id":"3d3e0a51-4e64-5fb8-b567-16b9a5993bf8","mechanism_event_label":"This downstream damage-response protein changed in the low-ascorbate culture condition.","subject":{"id":"15b3e015-2780-5848-a962-64c9f67e8087","slug":"chromate","display_name":"Chromate / chromium(VI) oxyanion","entity_type_key":"ion"},"object":{"id":"2b089152-4fa6-53c6-b752-41424374683b","slug":"chek2","display_name":"Human checkpoint kinase 2 / CHEK2","entity_type_key":"protein"},"evidence_count":1,"mechanism_event":{"id":"3d3e0a51-4e64-5fb8-b567-16b9a5993bf8","stable_key":"4d8e4781-3878-5818-8d0a-7dbd6e024555:chromium-chromate-chk2-event","event_type":"biochemical_relationship","label":"This downstream damage-response protein changed in the low-ascorbate culture condition.","description":"Chromate exposure induced CHK2 phosphorylation as part of the ATM response in standard ascorbate-poor human cell cultures.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"38d0c4d9-53d1-5239-bfe3-c1b5e9b79085","slug":"ascorbate","display_name":"L-Ascorbate","entity_type_key":"small_molecule"},"role":"availability_context","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"243ad948-2281-53f8-8e53-32247253668d","slug":"atm","display_name":"Human ATM kinase","entity_type_key":"protein"},"role":"upstream_kinase","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"15b3e015-2780-5848-a962-64c9f67e8087","slug":"chromate","display_name":"Chromate / chromium(VI) oxyanion","entity_type_key":"ion"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""},{"entity":{"id":"2b089152-4fa6-53c6-b752-41424374683b","slug":"chek2","display_name":"Human checkpoint kinase 2 / CHEK2","entity_type_key":"protein"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":3,"notes":""}]},"contexts":[{"dimension":"availability_state","value_text":"nutrient_deficiency","comparator":null,"unit":null,"notes":"Imported condition classification; unverified.","entity":null},{"dimension":"evidence_span","value_text":"{\"source_cache\": \"artifacts/chromium-research/25977998.abstract.txt\", \"locator\": \"Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"26c325e343b04aa77acf3164d848e8127c2d6a329ff0d9968426a12bde81d0b3\", \"start_char\": 0, \"end_char\": 2163, \"text_sha256\": \"26c325e343b04aa77acf3164d848e8127c2d6a329ff0d9968426a12bde81d0b3\"}","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Ascorbate restoration and ATM perturbation in human lung-cell cultures","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"Chromate exposure in standard ascorbate-poor versus ascorbate-restored cells; ATM inhibition/silencing","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Cr(VI) toxicology, not an experiment with dietary Cr(III). Loss of ATM activation does not mean loss of all genotoxicity or that vitamin C universally detoxifies chromium.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"Chromium research collection; topical membership is not evidence of a direct dietary effect.","comparator":null,"unit":null,"notes":"","entity":{"slug":"chromium","display_name":"Chromium","entity_type_key":"nutrient_element"}},{"dimension":"organism","value_text":"Human H460 cells and normal lung fibroblasts","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"This downstream damage-response protein changed in the low-ascorbate culture condition.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[chromium-p25977998] Different ATM Signaling in Response to Chromium(VI) Metabolism via Ascorbate and Nonascorbate Reduction: Implications for in Vitro Models and Toxicogenomics. (2016). https://pubmed.ncbi.nlm.nih.gov/25977998/ DOI: 10.1289/ehp.1409434","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue_or_cell_type","value_text":"DNA-damage signaling","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"trigger_kind","value_text":"nutrient_deficiency","comparator":null,"unit":null,"notes":"Imported condition classification; unverified.","entity":null}],"evidence":[{"id":"e1614050-7d88-56b5-a8cf-59e75f803c8e","evidence_kind":"source_excerpt","locator":"Lines 1134-1145","start_line":1134,"end_line":1145,"excerpt":"### chromium-chromate-chk2\nChromate exposure induced CHK2 phosphorylation as part of the ATM response in standard ascorbate-poor human cell cultures.\nCondition category: nutrient_deficiency\nnutrient_topic: Chromium research collection; topical membership is not evidence of a direct dietary effect.\nplain_language: This downstream damage-response protein changed in the low-ascorbate culture condition.\norganism: Human H460 cells and normal lung fibroblasts\ntissue_or_cell_type: DNA-damage signaling\nexperimental_model: Ascorbate restoration and ATM perturbation in human lung-cell cultures\nlimitations: Cr(VI) toxicology, not an experiment with dietary Cr(III). Loss of ATM activation does not mean loss of all genotoxicity or that vitamin C universally detoxifies chromium.\nexposure: Chromate exposure in standard ascorbate-poor versus ascorbate-restored cells; ATM inhibition/silencing\nevidence_span: {\"source_cache\": \"artifacts/chromium-research/25977998.abstract.txt\", \"locator\": \"Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"26c325e343b04aa77acf3164d848e8127c2d6a329ff0d9968426a12bde81d0b3\", \"start_char\": 0, \"end_char\": 2163, \"text_sha256\": \"26c325e343b04aa77acf3164d848e8127c2d6a329ff0d9968426a12bde81d0b3\"}\n[chromium-p25977998] Different ATM Signaling in Response to Chromium(VI) Metabolism via Ascorbate and Nonascorbate Reduction: Implications for in Vitro Models and Toxicogenomics. (2016). https://pubmed.ncbi.nlm.nih.gov/25977998/ DOI: 10.1289/ehp.1409434","model_system":"Ascorbate restoration and ATM perturbation in human lung-cell cultures","directness":"author_interpretation","verification_status":"source_derived_draft","notes":"Exact curation-document quotation, not publisher quotation. Study references: [chromium-p25977998] Different ATM Signaling in Response to Chromium(VI) Metabolism via Ascorbate and Nonascorbate Reduction: Implications for in Vitro Models and Toxicogenomics. 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