{"id":"95dfbc4c-d48d-5e3f-87ac-c98ebaf3ae1b","stable_key":"7484635e-cc8f-5cd6-a978-6dc5775a7db5:berberine-uhrf1-degradation","predicate":"promotes_degradation_of","statement":"Berberine promoted UHRF1 degradation and reduced its expression.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"context_dependent","is_public":true,"mechanism_event_id":"ef006108-9124-53c4-93d9-cacca9efb577","mechanism_event_label":"Removing a signaling regulator can help sustain AMPK activity.","subject":{"id":"7bbe0633-b2f1-510f-adc0-3c4d0ddad05d","slug":"berberine","display_name":"Berberine","entity_type_key":"small_molecule"},"object":{"id":"f77a6527-c60b-5f57-977d-341ca02689ef","slug":"uhrf1","display_name":"Human UHRF1","entity_type_key":"protein"},"evidence_count":1,"mechanism_event":{"id":"ef006108-9124-53c4-93d9-cacca9efb577","stable_key":"7484635e-cc8f-5cd6-a978-6dc5775a7db5:berberine-uhrf1-degradation-event","event_type":"biochemical_relationship","label":"Removing a signaling regulator can help sustain AMPK activity.","description":"Berberine promoted UHRF1 degradation and reduced its expression.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"7bbe0633-b2f1-510f-adc0-3c4d0ddad05d","slug":"berberine","display_name":"Berberine","entity_type_key":"small_molecule"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"f77a6527-c60b-5f57-977d-341ca02689ef","slug":"uhrf1","display_name":"Human UHRF1","entity_type_key":"protein"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""}]},"contexts":[{"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. Different dose/context from respiratory inhibition studies.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"Berberine research collection; topical membership is not evidence of a direct dietary effect.","comparator":null,"unit":null,"notes":"","entity":{"slug":"berberine","display_name":"Berberine","entity_type_key":"small_molecule"}},{"dimension":"organism","value_text":"Human HCT-116 cells","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"Removing a signaling regulator can help sustain AMPK activity.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[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","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}],"evidence":[{"id":"0091b4c3-fd12-5e4d-8823-a1f31f30274c","evidence_kind":"source_excerpt","locator":"Lines 389-400","start_line":389,"end_line":400,"excerpt":"### berberine-uhrf1-degradation\nBerberine promoted UHRF1 degradation and reduced its expression.\nCondition category: normal\nnutrient_topic: Berberine research collection; topical membership is not evidence of a direct dietary effect.\nplain_language: Removing a signaling regulator can help sustain AMPK activity.\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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