{"id":"1f56b743-91bb-55f7-97ff-5197ca0afdcc","stable_key":"44eaeae5-557a-552b-8998-884f30462e2a:sulforaphane-binding-not-release","predicate":"did_not_disrupt","statement":"Sulforaphane did not disrupt the KEAP1-Nrf2 association in the tested interaction assays.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"context_dependent","is_public":true,"mechanism_event_id":"a1405a99-1865-52c3-9a1c-7a1115bb8556","mechanism_event_label":"Activating this pathway did not require complete separation of these proteins in the assay.","subject":{"id":"67e70215-70c4-546a-84b4-0819fac0b326","slug":"sulforaphane","display_name":"Sulforaphane / SFN, stereochemistry specified per study","entity_type_key":"small_molecule"},"object":{"id":"45111a69-0318-55ea-8cdf-6f10e617ca64","slug":"keap1-nrf2-association","display_name":"KEAP1-Nrf2 association","entity_type_key":"cellular_process"},"evidence_count":1,"mechanism_event":{"id":"a1405a99-1865-52c3-9a1c-7a1115bb8556","stable_key":"44eaeae5-557a-552b-8998-884f30462e2a:sulforaphane-binding-not-release-event","event_type":"biochemical_relationship","label":"Activating this pathway did not require complete separation of these proteins in the assay.","description":"Sulforaphane did not disrupt the KEAP1-Nrf2 association in the tested interaction assays.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"c5b67b38-fe93-5e8f-91af-d77d3f590d98","slug":"keap1","display_name":"Human KEAP1","entity_type_key":"protein"},"role":"sensor_adaptor","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"3bf390ea-a550-5965-9e1e-ae36ce4cbc9a","slug":"cul3","display_name":"Human cullin 3 / CUL3","entity_type_key":"protein"},"role":"scaffold","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"515aa81c-e027-507a-90c9-8799fa46626c","slug":"rbx1","display_name":"Human RING-box protein 1 / RBX1","entity_type_key":"protein"},"role":"ligase_component","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""},{"entity":{"id":"dc472dd3-d383-567a-ab37-a9ec4e112df4","slug":"nfe2l2","display_name":"Human Nrf2 / NFE2L2","entity_type_key":"protein"},"role":"regulated_substrate","stoichiometry":null,"state_label":"","sequence_order":3,"notes":""},{"entity":{"id":"67e70215-70c4-546a-84b4-0819fac0b326","slug":"sulforaphane","display_name":"Sulforaphane / SFN, stereochemistry specified per study","entity_type_key":"small_molecule"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":4,"notes":""},{"entity":{"id":"45111a69-0318-55ea-8cdf-6f10e617ca64","slug":"keap1-nrf2-association","display_name":"KEAP1-Nrf2 association","entity_type_key":"cellular_process"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":5,"notes":""}]},"contexts":[{"dimension":"evidence_span","value_text":"{\"source_cache\": \"artifacts/sulforaphane-research/15572695.abstract.txt\", \"locator\": \"Primary indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"d120b0ea48a77a99b12e9147e4acb02fd63026ed729a37d5e2edf174c5674765\", \"start_char\": 0, \"end_char\": 1484, \"text_sha256\": \"d120b0ea48a77a99b12e9147e4acb02fd63026ed729a37d5e2edf174c5674765\"}","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Cell transfection, coimmunoprecipitation and ubiquitination assays","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"Sulforaphane or quinone stress; C151S KEAP1 comparison","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"The measured interaction is ubiquitin-ligase regulation; do not describe it as obligatory physical release of all bound Nrf2.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"Sulforaphane research collection; topical membership is not evidence of a direct dietary effect.","comparator":null,"unit":null,"notes":"","entity":{"slug":"sulforaphane","display_name":"Sulforaphane / SFN, stereochemistry specified per study","entity_type_key":"small_molecule"}},{"dimension":"organism","value_text":"Human protein constructs in mammalian cell systems","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"Activating this pathway did not require complete separation of these proteins in the assay.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[sulforaphane-p15572695] Keap1 is a redox-regulated substrate adaptor protein for a Cul3-dependent ubiquitin ligase complex. (2004). https://pubmed.ncbi.nlm.nih.gov/15572695/ DOI: 10.1128/mcb.24.24.10941-10953.2004","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue_or_cell_type","value_text":"KEAP1-CUL3-RBX1 control of Nrf2","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"ec878b6b-34b9-549a-816f-60344b325b0f","evidence_kind":"source_excerpt","locator":"Lines 489-500","start_line":489,"end_line":500,"excerpt":"### sulforaphane-binding-not-release\nSulforaphane did not disrupt the KEAP1-Nrf2 association in the tested interaction assays.\nCondition category: normal\nnutrient_topic: Sulforaphane research collection; topical membership is not evidence of a direct dietary effect.\nplain_language: Activating this pathway did not require complete separation of these proteins in the assay.\norganism: Human protein constructs in mammalian cell systems\ntissue_or_cell_type: KEAP1-CUL3-RBX1 control of Nrf2\nexperimental_model: Cell transfection, coimmunoprecipitation and ubiquitination assays\nlimitations: The measured interaction is ubiquitin-ligase regulation; do not describe it as obligatory physical release of all bound Nrf2.\nexposure: Sulforaphane or quinone stress; C151S KEAP1 comparison\nevidence_span: {\"source_cache\": \"artifacts/sulforaphane-research/15572695.abstract.txt\", \"locator\": \"Primary indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"d120b0ea48a77a99b12e9147e4acb02fd63026ed729a37d5e2edf174c5674765\", \"start_char\": 0, \"end_char\": 1484, \"text_sha256\": \"d120b0ea48a77a99b12e9147e4acb02fd63026ed729a37d5e2edf174c5674765\"}\n[sulforaphane-p15572695] Keap1 is a redox-regulated substrate adaptor protein for a Cul3-dependent ubiquitin ligase complex. 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