{"id":"ecd3a3f7-d232-5def-becd-6637fb0beed9","stable_key":"6d38d43e-01e4-5641-93be-65654271e242:zn-sig-gsh-mtf1-protection","predicate":"protected","statement":"Glutathione protected recombinant MTF1 from cadmium-mediated inactivation, allowing zinc-dependent DNA-binding activity in the assay.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"positive","is_public":true,"mechanism_event_id":"7ecb3549-eef3-5590-9454-50703546e6f2","mechanism_event_label":"Glutathione helped preserve the zinc-dependent sensor under this chemical stress.","subject":{"id":"b44c9e27-4bbb-52d3-a022-14cddded5073","slug":"glutathione","display_name":"GSH","entity_type_key":"small_molecule"},"object":{"id":"a2785dfa-f3a4-578e-ad13-7602cad6d828","slug":"mtf1-dna-binding","display_name":"MTF1 binding to metal-responsive DNA elements","entity_type_key":"cellular_process"},"evidence_count":1,"mechanism_event":{"id":"7ecb3549-eef3-5590-9454-50703546e6f2","stable_key":"6d38d43e-01e4-5641-93be-65654271e242:zn-sig-gsh-mtf1-protection-event","event_type":"biochemical_relationship","label":"Glutathione helped preserve the zinc-dependent sensor under this chemical stress.","description":"Glutathione protected recombinant MTF1 from cadmium-mediated inactivation, allowing zinc-dependent DNA-binding activity in the assay.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"1a6ae94b-21bd-5800-8eba-de39db9eeac9","slug":"mtf1","display_name":"Human metal-regulatory transcription factor 1 / MTF1","entity_type_key":"protein"},"role":"human_protein","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"e83dc538-b8b1-5528-9807-277f5b646893","slug":"mouse-mtf1","display_name":"Mouse metal-regulatory transcription factor 1 / Mtf1","entity_type_key":"protein"},"role":"mouse_protein","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"49c806c2-7041-5020-8b3b-fa04ffa122ac","slug":"zinc-ion","display_name":"Zinc(II) ion","entity_type_key":"ion"},"role":"activating_ion","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""},{"entity":{"id":"14a531bd-0c4f-5fdf-8596-d93cba4cb41f","slug":"cadmium-ion","display_name":"Cadmium(II) ion","entity_type_key":"ion"},"role":"inactivating_metal","stoichiometry":null,"state_label":"","sequence_order":3,"notes":""},{"entity":{"id":"b44c9e27-4bbb-52d3-a022-14cddded5073","slug":"glutathione","display_name":"GSH","entity_type_key":"small_molecule"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":4,"notes":""},{"entity":{"id":"a2785dfa-f3a4-578e-ad13-7602cad6d828","slug":"mtf1-dna-binding","display_name":"MTF1 binding to metal-responsive DNA elements","entity_type_key":"cellular_process"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":5,"notes":""}]},"contexts":[{"dimension":"cross_nutrient","value_text":"Human metal-regulatory transcription factor 1 / MTF1 (human_protein); Mouse metal-regulatory transcription factor 1 / Mtf1 (mouse_protein); Zinc(II) ion (activating_ion)","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"evidence_span","value_text":"{\"source_cache\": \"artifacts/zinc-signaling-sources/9507026-abstract.txt\", \"locator\": \"Primary indexed abstract\", \"file_sha256\": \"ecd19e16b15909d46328c2c5dcd9f9536422db7bb12b9dfd9d91763fafe164bd\"}","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Human and mouse cell extracts and recombinant MTF1","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"Zinc versus other tested transition metals; DNA-binding assays. Glutathione was 1 mM in the recombinant-protein cadmium challenge; this is an in-vitro assay concentration.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"In-vitro metal specificity does not mean all cellular metal responses are mediated by direct MTF1 binding.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"Zinc research collection; topical membership is not evidence of a direct dietary effect.","comparator":null,"unit":null,"notes":"","entity":{"slug":"zinc","display_name":"Zinc","entity_type_key":"nutrient_element"}},{"dimension":"organism","value_text":"Homo sapiens; Mus musculus","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"Glutathione helped preserve the zinc-dependent sensor under this chemical stress.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[zn-sig-9507026] The DNA binding activity of metal response element-binding transcription factor-1 is activated in vivo and in vitro by zinc, but not by other transition metals. (1998). https://pubmed.ncbi.nlm.nih.gov/9507026/ DOI: 10.1074/jbc.273.12.7127","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue_or_cell_type","value_text":"Cell extracts and recombinant protein","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"e08d5cfd-2390-54a0-8fec-368433b93c79","evidence_kind":"source_excerpt","locator":"Lines 887-899","start_line":887,"end_line":899,"excerpt":"### zn-sig-gsh-mtf1-protection\nGlutathione protected recombinant MTF1 from cadmium-mediated inactivation, allowing zinc-dependent DNA-binding activity in the assay.\nCondition category: normal\nnutrient_topic: Zinc research collection; topical membership is not evidence of a direct dietary effect.\nplain_language: Glutathione helped preserve the zinc-dependent sensor under this chemical stress.\norganism: Homo sapiens; Mus musculus\ntissue_or_cell_type: Cell extracts and recombinant protein\nexperimental_model: Human and mouse cell extracts and recombinant MTF1\nlimitations: In-vitro metal specificity does not mean all cellular metal responses are mediated by direct MTF1 binding.\nexposure: Zinc versus other tested transition metals; DNA-binding assays. Glutathione was 1 mM in the recombinant-protein cadmium challenge; this is an in-vitro assay concentration.\ncross_nutrient: Human metal-regulatory transcription factor 1 / MTF1 (human_protein); Mouse metal-regulatory transcription factor 1 / Mtf1 (mouse_protein); Zinc(II) ion (activating_ion)\nevidence_span: {\"source_cache\": \"artifacts/zinc-signaling-sources/9507026-abstract.txt\", \"locator\": \"Primary indexed abstract\", \"file_sha256\": \"ecd19e16b15909d46328c2c5dcd9f9536422db7bb12b9dfd9d91763fafe164bd\"}\n[zn-sig-9507026] The DNA binding activity of metal response element-binding transcription factor-1 is activated in vivo and in vitro by zinc, but not by other transition metals. (1998). https://pubmed.ncbi.nlm.nih.gov/9507026/ DOI: 10.1074/jbc.273.12.7127","model_system":"Human and mouse cell extracts and recombinant MTF1","directness":"author_interpretation","verification_status":"source_derived_draft","notes":"Exact curation-document quotation, not publisher quotation. Study references: [zn-sig-9507026] The DNA binding activity of metal response element-binding transcription factor-1 is activated in vivo and in vitro by zinc, but not by other transition metals. (1998). https://pubmed.ncbi.nlm.nih.gov/9507026/ DOI: 10.1074/jbc.273.12.7127","relationship":"supports","weight":1.0,"link_notes":"","source":{"id":"c5ee0fee-ce5c-58de-905a-10fb0ea0723c","stable_key":"import-6d38d43e-01e4-5641-93be-65654271e242","title":"Zinc: transport, enzyme loading, deficiency and nutrient interactions (2026-09-17)","document_type":"imported_text","citation_label":"AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text.","file_path":"","sha256":"2e731dd54477ec1254e97df3323e1208d38f1375effed19252e71ab4f600d13a","revision_id":"c72258b9-ac09-5408-9d44-a921ad1f96a3","review_status":"unverified_draft","notes":""}}],"relations":[],"conflicts":[],"corrections":[],"research":null}