{"id":"258e2e29-4164-5699-a1c3-8386df7c0db8","stable_key":"7484635e-cc8f-5cd6-a978-6dc5775a7db5:berberine-axin1-loss","predicate":"loss_impairs_berberine_activation_of","statement":"AXIN1 loss impaired the berberine response of lysosomal AMPK.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"context_dependent","is_public":true,"mechanism_event_id":"fbaf0da3-e663-5a11-832a-04f8b9641d19","mechanism_event_label":"This branch cannot operate normally without its scaffold.","subject":{"id":"3686ac61-7055-5c88-a3b9-adc0851efa1d","slug":"axin1","display_name":"Human AXIN1","entity_type_key":"protein"},"object":{"id":"7a01190d-4397-5a6f-944d-69a9d2e9b8c7","slug":"lysosomal-ampk-activity","display_name":"Lysosome-associated AMPK activity","entity_type_key":"cellular_process"},"evidence_count":1,"mechanism_event":{"id":"fbaf0da3-e663-5a11-832a-04f8b9641d19","stable_key":"7484635e-cc8f-5cd6-a978-6dc5775a7db5:berberine-axin1-loss-event","event_type":"biochemical_relationship","label":"This branch cannot operate normally without its scaffold.","description":"AXIN1 loss impaired the berberine response of lysosomal AMPK.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"7bbe0633-b2f1-510f-adc0-3c4d0ddad05d","slug":"berberine","display_name":"Berberine","entity_type_key":"small_molecule"},"role":"exposure","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"3686ac61-7055-5c88-a3b9-adc0851efa1d","slug":"axin1","display_name":"Human AXIN1","entity_type_key":"protein"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"7a01190d-4397-5a6f-944d-69a9d2e9b8c7","slug":"lysosomal-ampk-activity","display_name":"Lysosome-associated AMPK activity","entity_type_key":"cellular_process"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":2,"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/berberine-research/37144221.abstract.txt\", \"locator\": \"Primary indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"e146553474cca4ec8441b54580959225dcf3dfee60a50ea519ccac5e2cb6488d\", \"start_char\": 0, \"end_char\": 1212, \"text_sha256\": \"e146553474cca4ec8441b54580959225dcf3dfee60a50ea519ccac5e2cb6488d\"}","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Lysosome isolation, genetic perturbation and coimmunoprecipitation","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"Low-dose berberine experiments; AXIN1 loss, PEN2 perturbation and UHRF1 overexpression","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Cancer-cell signaling model; low laboratory concentration is not proof of a mechanism at every human tissue exposure. 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(2023). https://pubmed.ncbi.nlm.nih.gov/37144221/ DOI: 10.3389/fphar.2023.1148611","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue_or_cell_type","value_text":"Lysosomal AMPK and UHRF1 regulation","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":"2cf7b4bf-28c7-51d9-abeb-9677a05f610c","evidence_kind":"source_excerpt","locator":"Lines 415-426","start_line":415,"end_line":426,"excerpt":"### berberine-axin1-loss\nAXIN1 loss impaired the berberine response of lysosomal AMPK.\nCondition category: machinery_impairment\nnutrient_topic: Berberine research collection; topical membership is not evidence of a direct dietary effect.\nplain_language: This branch cannot operate normally without its scaffold.\norganism: Human HCT-116 cells\ntissue_or_cell_type: Lysosomal AMPK and UHRF1 regulation\nexperimental_model: Lysosome isolation, genetic perturbation and coimmunoprecipitation\nlimitations: Cancer-cell signaling model; low laboratory concentration is not proof of a mechanism at every human tissue exposure. Different dose/context from respiratory inhibition studies.\nexposure: Low-dose berberine experiments; AXIN1 loss, PEN2 perturbation and UHRF1 overexpression\nevidence_span: {\"source_cache\": \"artifacts/berberine-research/37144221.abstract.txt\", \"locator\": \"Primary indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"e146553474cca4ec8441b54580959225dcf3dfee60a50ea519ccac5e2cb6488d\", \"start_char\": 0, \"end_char\": 1212, \"text_sha256\": \"e146553474cca4ec8441b54580959225dcf3dfee60a50ea519ccac5e2cb6488d\"}\n[berberine-p37144221] Berberine stimulates lysosomal AMPK independent of PEN2 and maintains cellular AMPK activity through inhibiting the dephosphorylation regulator UHRF1. (2023). https://pubmed.ncbi.nlm.nih.gov/37144221/ DOI: 10.3389/fphar.2023.1148611","model_system":"Lysosome isolation, genetic perturbation and coimmunoprecipitation","directness":"author_interpretation","verification_status":"source_derived_draft","notes":"Exact curation-document quotation, not publisher quotation. Study references: [berberine-p37144221] Berberine stimulates lysosomal AMPK independent of PEN2 and maintains cellular AMPK activity through inhibiting the dephosphorylation regulator UHRF1. 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