{"id":"75772951-f762-57e4-ae62-b86c323c81db","stable_key":"2921131d-0ba0-51d3-8f59-8c4be3b9ac08:cucurbitacin-i-rhoa-rock","predicate":"activates_tested","statement":"Cucurbitacin I activated RhoA/ROCK signaling; disrupting this pathway prevented the observed Rac1 inhibition.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"context_dependent","is_public":true,"mechanism_event_id":"9a998e9f-04fe-59fa-bd0c-8ea4fa909d4b","mechanism_event_label":"One cytoskeletal pathway helped suppress another.","subject":{"id":"55ef0ba6-495d-5cc4-88c5-0772ab25d0fe","slug":"cucurbitacin-i","display_name":"Cucurbitacin I","entity_type_key":"small_molecule"},"object":{"id":"d49271fa-2950-5fdf-bd85-a3411b79c3f2","slug":"human-rhoa","display_name":"Human RhoA / RHOA","entity_type_key":"protein"},"evidence_count":1,"mechanism_event":{"id":"9a998e9f-04fe-59fa-bd0c-8ea4fa909d4b","stable_key":"2921131d-0ba0-51d3-8f59-8c4be3b9ac08:cucurbitacin-i-rhoa-rock-event","event_type":"observed_relationship","label":"One cytoskeletal pathway helped suppress another.","description":"Cucurbitacin I activated RhoA/ROCK signaling; disrupting this pathway prevented the observed Rac1 inhibition.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"55ef0ba6-495d-5cc4-88c5-0772ab25d0fe","slug":"cucurbitacin-i","display_name":"Cucurbitacin I","entity_type_key":"small_molecule"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"d49271fa-2950-5fdf-bd85-a3411b79c3f2","slug":"human-rhoa","display_name":"Human RhoA / RHOA","entity_type_key":"protein"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"9343b9ca-72ab-5e41-84a8-9b36aca329d5","slug":"human-rock-family","display_name":"Human Rho-associated kinases, isoform unresolved","entity_type_key":"protein_family"},"role":"context_participant","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""},{"entity":{"id":"8a96d7c7-d28d-5615-94a7-3c397bed8f9d","slug":"rac1","display_name":"RAC1","entity_type_key":"protein"},"role":"context_participant","stoichiometry":null,"state_label":"","sequence_order":3,"notes":""}]},"contexts":[{"dimension":"evidence_access","value_text":"Primary abstract","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Human breast-cancer cellular perturbation experiments.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"ROCK isoform is not resolved in this record; pathway dependence does not establish a direct cucurbitacin target.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"Cucurbitacins collection; species, compartment, exposure, co-substrates and manipulation remain explicit.","comparator":null,"unit":null,"notes":"","entity":{"slug":"cucurbitacin","display_name":"Cucurbitacins","entity_type_key":"chemical_species"}},{"dimension":"plain_language","value_text":"One cytoskeletal pathway helped suppress another.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"Cucurbitacin I inhibits Rac1 activation in breast cancer cells by a reactive oxygen species-mediated mechanism and independently of Janus tyrosine kinase 2 and P-Rex1. · 2013 · https://pubmed.ncbi.nlm.nih.gov/23478800/ · DOI 10.1124/mol.112.084293","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"250b234f-5b5d-5b7e-a2ec-efa44c902efe","evidence_kind":"source_excerpt","locator":"Lines 164-170","start_line":164,"end_line":170,"excerpt":"## cucurbitacin-i-rhoa-rock\nOne cytoskeletal pathway helped suppress another.\nCucurbitacin I activated RhoA/ROCK signaling; disrupting this pathway prevented the observed Rac1 inhibition.\nModel: Human breast-cancer cellular perturbation experiments.\nLimitations: ROCK isoform is not resolved in this record; pathway dependence does not establish a direct cucurbitacin target.\nEvidence access: Primary abstract\nCucurbitacin I inhibits Rac1 activation in breast cancer cells by a reactive oxygen species-mediated mechanism and independently of Janus tyrosine kinase 2 and P-Rex1. · 2013 · https://pubmed.ncbi.nlm.nih.gov/23478800/ · DOI 10.1124/mol.112.084293","model_system":"Human breast-cancer cellular perturbation experiments.","directness":"reported_statement","verification_status":"source_derived_draft","notes":"Original curation paraphrase; evidence access and experimental limitations specified.","relationship":"supports","weight":1.0,"link_notes":"","source":{"id":"77324310-00ce-5d28-9fc7-595fddae86b9","stable_key":"import-2921131d-0ba0-51d3-8f59-8c4be3b9ac08","title":"Cucurbitacins: thiol chemistry, cytoskeleton, metabolic dependencies and signaling (2026-09-20)","document_type":"imported_text","citation_label":"AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text.","file_path":"","sha256":"5c23ec61b9cf3d2966fb081d8617e1e1f7c522e86419b8ba2dcae09590121123","revision_id":"74251a06-3ba5-506c-b428-700eca0fb432","review_status":"unverified_draft","notes":""}}],"relations":[],"conflicts":[],"corrections":[],"research":null}