{"id":"ef7477d8-74c3-51dd-b2f4-6113f08623a0","stable_key":"aaa7baba-8689-56ab-ba1e-b71542bcb8e9:i-met-t3-thrb-transcription","predicate":"increases","statement":"T3 increased thyroid-response-element luciferase activity in CV-1 cells transfected with full-length human THRB and RXRA.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"positive","is_public":true,"mechanism_event_id":"84d689ef-5b57-5639-9e21-f7a1b6678b5f","mechanism_event_label":"Binding of the hormone can be translated into a gene-regulatory signal through its receptor.","subject":{"id":"559f37d2-ee0a-589b-8689-fa80ca9ae653","slug":"triiodothyronine","display_name":"T3","entity_type_key":"small_molecule"},"object":{"id":"e6dc5efa-f7bd-5297-a7c6-3f29c5521fc2","slug":"dr4-thyroid-response-reporter-activity","display_name":"DR4 thyroid-response-element reporter activity","entity_type_key":"cellular_process"},"evidence_count":1,"mechanism_event":{"id":"84d689ef-5b57-5639-9e21-f7a1b6678b5f","stable_key":"aaa7baba-8689-56ab-ba1e-b71542bcb8e9:i-met-t3-thrb-transcription-event","event_type":"biochemical_relationship","label":"Binding of the hormone can be translated into a gene-regulatory signal through its receptor.","description":"T3 increased thyroid-response-element luciferase activity in CV-1 cells transfected with full-length human THRB and RXRA.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"559f37d2-ee0a-589b-8689-fa80ca9ae653","slug":"triiodothyronine","display_name":"T3","entity_type_key":"small_molecule"},"role":"ligand","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"012e6f8c-edb7-5962-bdc9-a075c7742137","slug":"thrb","display_name":"Thyroid hormone receptor beta","entity_type_key":"protein"},"role":"receptor","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"7dc1ce11-f208-5187-95d9-96b07927df6a","slug":"rxra","display_name":"Retinoid X receptor alpha","entity_type_key":"protein"},"role":"heterodimer_partner","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""},{"entity":{"id":"e6dc5efa-f7bd-5297-a7c6-3f29c5521fc2","slug":"dr4-thyroid-response-reporter-activity","display_name":"DR4 thyroid-response-element reporter activity","entity_type_key":"cellular_process"},"role":"transcriptional_readout","stoichiometry":null,"state_label":"","sequence_order":3,"notes":""}]},"contexts":[{"dimension":"cross_nutrient","value_text":"Human thyroid and retinoid receptor machinery jointly support the measured iodine-containing-hormone response; this does not establish dietary vitamin A dependence.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"evidence_locator","value_text":"Figure 1b and legend; Methods: Cell-based assays","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"evidence_spans","value_text":"[{\"source_document\": \"artifacts/iodine-metabolism-sources/26289479.txt\", \"locator\": \"Figure 1b and legend; Methods: Cell-based assays\", \"start_char\": 45264, \"end_char\": 46014}]","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Human TR beta/RXR alpha ligand-binding-domain crystallography; full-length human receptors in CV-1 reporter assays","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"1 micromolar T3 for 24 hours versus vehicle, with THRB/RXRA expression plasmids and a DR4 thyroid-response luciferase reporter; quadruplicate wells and at least two experiments.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Engineered reporter and receptor overexpression; cannot infer that every endogenous gene is activated by T3 or that dietary iodine or vitamin A improves this signal.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"Iodine research collection; topical membership is not evidence of a direct dietary effect.","comparator":null,"unit":null,"notes":"","entity":{"slug":"iodine","display_name":"Iodine","entity_type_key":"nutrient_element"}},{"dimension":"organism","value_text":"Full-length human receptors expressed in African green monkey CV-1 cells","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"Binding of the hormone can be translated into a gene-regulatory signal through its receptor.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[i-met-26289479] Structural mechanism for signal transduction in RXR nuclear receptor heterodimers. (2015). https://pubmed.ncbi.nlm.nih.gov/26289479/ DOI: 10.1038/ncomms9013","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue_or_cell_type","value_text":"CV-1 reporter assay","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"7f9d6a06-e74b-53a0-88c9-aba41ac37f9d","evidence_kind":"source_excerpt","locator":"Lines 1187-1200","start_line":1187,"end_line":1200,"excerpt":"### i-met-t3-thrb-transcription\nT3 increased thyroid-response-element luciferase activity in CV-1 cells transfected with full-length human THRB and RXRA.\nCondition category: normal\nnutrient_topic: Iodine research collection; topical membership is not evidence of a direct dietary effect.\nplain_language: Binding of the hormone can be translated into a gene-regulatory signal through its receptor.\norganism: Full-length human receptors expressed in African green monkey CV-1 cells\ntissue_or_cell_type: CV-1 reporter assay\nexperimental_model: Human TR beta/RXR alpha ligand-binding-domain crystallography; full-length human receptors in CV-1 reporter assays\nlimitations: Engineered reporter and receptor overexpression; cannot infer that every endogenous gene is activated by T3 or that dietary iodine or vitamin A improves this signal.\nexposure: 1 micromolar T3 for 24 hours versus vehicle, with THRB/RXRA expression plasmids and a DR4 thyroid-response luciferase reporter; quadruplicate wells and at least two experiments.\ncross_nutrient: Human thyroid and retinoid receptor machinery jointly support the measured iodine-containing-hormone response; this does not establish dietary vitamin A dependence.\nevidence_locator: Figure 1b and legend; Methods: Cell-based assays\nevidence_spans: [{\"source_document\": \"artifacts/iodine-metabolism-sources/26289479.txt\", \"locator\": \"Figure 1b and legend; Methods: Cell-based assays\", \"start_char\": 45264, \"end_char\": 46014}]\n[i-met-26289479] Structural mechanism for signal transduction in RXR nuclear receptor heterodimers. 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