{"id":"99829dd5-00ab-57d6-82a5-b97c16ca1767","stable_key":"6612c190-1948-5bcf-bbe3-a7f6c50fa3cf:l-proline-pycr1-hypoxic-loss","predicate":"supports","statement":"PYCR1 loss increased hypoxia-associated cell death in three-dimensional cancer cultures and tumors in vivo.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"positive","is_public":true,"mechanism_event_id":"b1b5e103-55bb-5121-b4ce-17b8ba4646e7","mechanism_event_label":"A cell may need the synthesis reaction itself, not merely a measured pool of the final amino acid.","subject":{"id":"6a5e6627-f4fd-5a02-b74b-371b629b076b","slug":"pycr1","display_name":"Human pyrroline-5-carboxylate reductase 1 / PYCR1","entity_type_key":"protein"},"object":{"id":"8f5540ce-d3db-5472-b95a-1cd8ec086bf6","slug":"human-pycr1-hypoxic-survival","display_name":"Hypoxic survival of PYCR1-manipulated human cancer cells","entity_type_key":"cellular_process"},"evidence_count":1,"mechanism_event":{"id":"b1b5e103-55bb-5121-b4ce-17b8ba4646e7","stable_key":"6612c190-1948-5bcf-bbe3-a7f6c50fa3cf:l-proline-pycr1-hypoxic-loss-event","event_type":"observed_relationship","label":"A cell may need the synthesis reaction itself, not merely a measured pool of the final amino acid.","description":"PYCR1 loss increased hypoxia-associated cell death in three-dimensional cancer cultures and tumors in vivo.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"6a5e6627-f4fd-5a02-b74b-371b629b076b","slug":"pycr1","display_name":"Human pyrroline-5-carboxylate reductase 1 / PYCR1","entity_type_key":"protein"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"8f5540ce-d3db-5472-b95a-1cd8ec086bf6","slug":"human-pycr1-hypoxic-survival","display_name":"Hypoxic survival of PYCR1-manipulated human cancer cells","entity_type_key":"cellular_process"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"70ccd53c-83ad-5251-a4f5-6370973bc40a","slug":"l-proline","display_name":"L-Proline","entity_type_key":"small_molecule"},"role":"context_participant","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""}]},"contexts":[{"dimension":"availability_state","value_text":"machinery_impairment","comparator":null,"unit":null,"notes":"Imported condition classification; 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unverified.","entity":null}],"evidence":[{"id":"0eda538c-4540-577f-859d-8fcd249b289a","evidence_kind":"source_excerpt","locator":"Lines 358-364","start_line":358,"end_line":364,"excerpt":"## l-proline-pycr1-hypoxic-loss\nA cell may need the synthesis reaction itself, not merely a measured pool of the final amino acid.\nPYCR1 loss increased hypoxia-associated cell death in three-dimensional cancer cultures and tumors in vivo.\nModel: Human cancer-cell PYCR1 depletion/knockout and xenograft experiments.\nLimitations: This is a context-specific vulnerability and is not proof of systemic proline deficiency.\nEvidence access: Primary full text\nProline synthesis through PYCR1 is required to support cancer cell proliferation and survival in oxygen-limiting conditions. · 2022 · https://pubmed.ncbi.nlm.nih.gov/35108535/ · DOI 10.1016/j.celrep.2022.110320","model_system":"Human cancer-cell PYCR1 depletion/knockout and xenograft experiments.","directness":"reported_statement","verification_status":"source_derived_draft","notes":"Original curation paraphrase; 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