{"id":"f90fde79-b4e6-5a45-af0b-966cba6da2ef","stable_key":"44eaeae5-557a-552b-8998-884f30462e2a:sulforaphane-c151s-response","predicate":"resisted_sulforaphane_inhibition_of","statement":"KEAP1 C151S was markedly resistant to sulforaphane inhibition of its Nrf2-ubiquitination function.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"context_dependent","is_public":true,"mechanism_event_id":"f29035fe-02c5-523c-8b56-cdf2baa01058","mechanism_event_label":"An altered sensor can block the response even when the compound is present.","subject":{"id":"b9d8256c-f96c-574e-b9cf-5538413a760e","slug":"keap1-c151s","display_name":"Human KEAP1 C151S variant","entity_type_key":"protein_state"},"object":{"id":"0f495f1a-3314-54bd-8960-b35c6f5d7a69","slug":"nrf2-ubiquitination","display_name":"KEAP1-dependent Nrf2 ubiquitination","entity_type_key":"cellular_process"},"evidence_count":1,"mechanism_event":{"id":"f29035fe-02c5-523c-8b56-cdf2baa01058","stable_key":"44eaeae5-557a-552b-8998-884f30462e2a:sulforaphane-c151s-response-event","event_type":"biochemical_relationship","label":"An altered sensor can block the response even when the compound is present.","description":"KEAP1 C151S was markedly resistant to sulforaphane inhibition of its Nrf2-ubiquitination function.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"67e70215-70c4-546a-84b4-0819fac0b326","slug":"sulforaphane","display_name":"Sulforaphane / SFN, stereochemistry specified per study","entity_type_key":"small_molecule"},"role":"exposure","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"dc472dd3-d383-567a-ab37-a9ec4e112df4","slug":"nfe2l2","display_name":"Human Nrf2 / NFE2L2","entity_type_key":"protein"},"role":"downstream_regulator","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"b9d8256c-f96c-574e-b9cf-5538413a760e","slug":"keap1-c151s","display_name":"Human KEAP1 C151S variant","entity_type_key":"protein_state"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""},{"entity":{"id":"0f495f1a-3314-54bd-8960-b35c6f5d7a69","slug":"nrf2-ubiquitination","display_name":"KEAP1-dependent Nrf2 ubiquitination","entity_type_key":"cellular_process"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":3,"notes":""}]},"contexts":[{"dimension":"availability_state","value_text":"machinery_impairment","comparator":null,"unit":null,"notes":"Imported condition classification; unverified.","entity":null},{"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":"An altered sensor can block the response even when the compound is present.","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},{"dimension":"trigger_kind","value_text":"machinery_impairment","comparator":null,"unit":null,"notes":"Imported condition classification; unverified.","entity":null}],"evidence":[{"id":"ce83eff3-964a-57b6-8cae-11060e657899","evidence_kind":"source_excerpt","locator":"Lines 502-513","start_line":502,"end_line":513,"excerpt":"### sulforaphane-c151s-response\nKEAP1 C151S was markedly resistant to sulforaphane inhibition of its Nrf2-ubiquitination function.\nCondition category: machinery_impairment\nnutrient_topic: Sulforaphane research collection; topical membership is not evidence of a direct dietary effect.\nplain_language: An altered sensor can block the response even when the compound is present.\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. (2004). https://pubmed.ncbi.nlm.nih.gov/15572695/ DOI: 10.1128/mcb.24.24.10941-10953.2004","model_system":"Cell transfection, coimmunoprecipitation and ubiquitination assays","directness":"author_interpretation","verification_status":"source_derived_draft","notes":"Exact curation-document quotation, not publisher quotation. Study references: [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","relationship":"supports","weight":1.0,"link_notes":"","source":{"id":"a4bafbf7-f117-53c9-a6d7-8fb25e4aca72","stable_key":"import-44eaeae5-557a-552b-8998-884f30462e2a","title":"Sulforaphane: formation, electrophile sensing and nutrient connections (2026-09-17)","document_type":"imported_text","citation_label":"AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. 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