{"id":"5ac325bd-b5cf-5c5c-b776-696004b7f75a","stable_key":"44eaeae5-557a-552b-8998-884f30462e2a:sulforaphane-nrf2-stability","predicate":"increased","statement":"Sulforaphane enabled Nrf2 to escape KEAP1-dependent degradation and increased its stability.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"context_dependent","is_public":true,"mechanism_event_id":"71037a3e-f777-5183-a6a6-5567e8db5b84","mechanism_event_label":"The cell keeps more of the regulator available.","subject":{"id":"67e70215-70c4-546a-84b4-0819fac0b326","slug":"sulforaphane","display_name":"Sulforaphane / SFN, stereochemistry specified per study","entity_type_key":"small_molecule"},"object":{"id":"11d255d4-1166-5864-acf3-4bb5bc5de59b","slug":"nrf2-protein-stability","display_name":"Nrf2 protein stability","entity_type_key":"cellular_process"},"evidence_count":1,"mechanism_event":{"id":"71037a3e-f777-5183-a6a6-5567e8db5b84","stable_key":"44eaeae5-557a-552b-8998-884f30462e2a:sulforaphane-nrf2-stability-event","event_type":"biochemical_relationship","label":"The cell keeps more of the regulator available.","description":"Sulforaphane enabled Nrf2 to escape KEAP1-dependent degradation and increased its stability.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"dc472dd3-d383-567a-ab37-a9ec4e112df4","slug":"nfe2l2","display_name":"Human Nrf2 / NFE2L2","entity_type_key":"protein"},"role":"transcription_factor","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"c5b67b38-fe93-5e8f-91af-d77d3f590d98","slug":"keap1","display_name":"Human KEAP1","entity_type_key":"protein"},"role":"upstream_sensor","stoichiometry":null,"state_label":"","sequence_order":1,"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":2,"notes":""},{"entity":{"id":"11d255d4-1166-5864-acf3-4bb5bc5de59b","slug":"nrf2-protein-stability","display_name":"Nrf2 protein stability","entity_type_key":"cellular_process"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":3,"notes":""}]},"contexts":[{"dimension":"evidence_span","value_text":"{\"source_cache\": \"artifacts/sulforaphane-research/14585973.abstract.txt\", \"locator\": \"Primary indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"bc2e1304879d9bd3d1b4946981f93a78d3f604c580ea252af17f645e237cadd0\", \"start_char\": 0, \"end_char\": 1647, \"text_sha256\": \"bc2e1304879d9bd3d1b4946981f93a78d3f604c580ea252af17f645e237cadd0\"}","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"KEAP1 mutagenesis and Nrf2 stability/localization assays","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"Sulforaphane or oxidative stress; C151/C273/C288 variants","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Individual cysteines have different roles; activating Nrf2 does not establish prevention or treatment of cancer in humans.","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 KEAP1 constructs in cellular experiments","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"The cell keeps more of the regulator available.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[sulforaphane-p14585973] Distinct cysteine residues in Keap1 are required for Keap1-dependent ubiquitination of Nrf2 and for stabilization of Nrf2 by chemopreventive agents and oxidative stress. (2003). https://pubmed.ncbi.nlm.nih.gov/14585973/ DOI: 10.1128/mcb.23.22.8137-8151.2003","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue_or_cell_type","value_text":"Ubiquitination, protein turnover and nuclear localization","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"8b631de2-852d-59d8-8cea-1e4086fdc39b","evidence_kind":"source_excerpt","locator":"Lines 515-526","start_line":515,"end_line":526,"excerpt":"### sulforaphane-nrf2-stability\nSulforaphane enabled Nrf2 to escape KEAP1-dependent degradation and increased its stability.\nCondition category: normal\nnutrient_topic: Sulforaphane research collection; topical membership is not evidence of a direct dietary effect.\nplain_language: The cell keeps more of the regulator available.\norganism: Human KEAP1 constructs in cellular experiments\ntissue_or_cell_type: Ubiquitination, protein turnover and nuclear localization\nexperimental_model: KEAP1 mutagenesis and Nrf2 stability/localization assays\nlimitations: Individual cysteines have different roles; activating Nrf2 does not establish prevention or treatment of cancer in humans.\nexposure: Sulforaphane or oxidative stress; C151/C273/C288 variants\nevidence_span: {\"source_cache\": \"artifacts/sulforaphane-research/14585973.abstract.txt\", \"locator\": \"Primary indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"bc2e1304879d9bd3d1b4946981f93a78d3f604c580ea252af17f645e237cadd0\", \"start_char\": 0, \"end_char\": 1647, \"text_sha256\": \"bc2e1304879d9bd3d1b4946981f93a78d3f604c580ea252af17f645e237cadd0\"}\n[sulforaphane-p14585973] Distinct cysteine residues in Keap1 are required for Keap1-dependent ubiquitination of Nrf2 and for stabilization of Nrf2 by chemopreventive agents and oxidative stress. (2003). https://pubmed.ncbi.nlm.nih.gov/14585973/ DOI: 10.1128/mcb.23.22.8137-8151.2003","model_system":"KEAP1 mutagenesis and Nrf2 stability/localization assays","directness":"author_interpretation","verification_status":"source_derived_draft","notes":"Exact curation-document quotation, not publisher quotation. Study references: [sulforaphane-p14585973] Distinct cysteine residues in Keap1 are required for Keap1-dependent ubiquitination of Nrf2 and for stabilization of Nrf2 by chemopreventive agents and oxidative stress. (2003). https://pubmed.ncbi.nlm.nih.gov/14585973/ DOI: 10.1128/mcb.23.22.8137-8151.2003","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. Not publisher full text.","file_path":"","sha256":"f355c492a6c35673d8260b1328667fe206e5315b9fcaa5aeff53d80373c7ef97","revision_id":"f2c47d71-34cd-5160-8e92-fe196b576707","review_status":"unverified_draft","notes":""}}],"relations":[],"conflicts":[],"corrections":[],"research":null}