{"id":"65b23a4c-5d51-583f-96cb-d76a130a5bde","stable_key":"e37461ea-ea5d-5e2c-8091-138305f6dd70:l-aspartate-cad-s6k1","predicate":"phosphorylates","statement":"S6K1 directly phosphorylated CAD at Ser1859, connecting mTORC1 signaling to increased de novo pyrimidine synthesis.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"context_dependent","is_public":true,"mechanism_event_id":"f6f7b12e-55d0-5714-b618-808249501643","mechanism_event_label":"Growth signals can accelerate use of aspartate for nucleotide production.","subject":{"id":"d357f815-7928-5fb8-a704-b526b6d6aa28","slug":"rps6kb1","display_name":"Human p70 S6 kinase / RPS6KB1","entity_type_key":"protein"},"object":{"id":"64cc3b93-3e99-5221-bd91-049d190e54c7","slug":"cad","display_name":"Human CAD multifunctional pyrimidine synthesis enzyme","entity_type_key":"protein"},"evidence_count":1,"mechanism_event":{"id":"f6f7b12e-55d0-5714-b618-808249501643","stable_key":"e37461ea-ea5d-5e2c-8091-138305f6dd70:l-aspartate-cad-s6k1-event","event_type":"observed_relationship","label":"Growth signals can accelerate use of aspartate for nucleotide production.","description":"S6K1 directly phosphorylated CAD at Ser1859, connecting mTORC1 signaling to increased de novo pyrimidine synthesis.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"d357f815-7928-5fb8-a704-b526b6d6aa28","slug":"rps6kb1","display_name":"Human p70 S6 kinase / RPS6KB1","entity_type_key":"protein"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"64cc3b93-3e99-5221-bd91-049d190e54c7","slug":"cad","display_name":"Human CAD multifunctional pyrimidine synthesis enzyme","entity_type_key":"protein"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"0a0923d3-72b7-5d6a-bf3a-5a7a3071a09b","slug":"l-aspartate","display_name":"L-Aspartate","entity_type_key":"small_molecule"},"role":"context_participant","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""},{"entity":{"id":"9f025af3-f039-517f-908b-4af6fc65415e","slug":"mtorc1","display_name":"Mechanistic target of rapamycin complex 1","entity_type_key":"protein_complex"},"role":"context_participant","stoichiometry":null,"state_label":"","sequence_order":3,"notes":""},{"entity":{"id":"8637bb39-2c30-5168-baaf-3e613d831db0","slug":"glutamine","display_name":"L-Glutamine","entity_type_key":"small_molecule"},"role":"context_participant","stoichiometry":null,"state_label":"","sequence_order":4,"notes":""},{"entity":{"id":"58b974f1-d389-5bf6-81cd-889c44442c42","slug":"atp","display_name":"ATP","entity_type_key":"small_molecule"},"role":"context_participant","stoichiometry":null,"state_label":"","sequence_order":5,"notes":""}]},"contexts":[{"dimension":"evidence_access","value_text":"Primary full text","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Human HEK293E CAD expression, phosphosite mutation and kinase assays; complementary mouse cell tracing.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"This is a signaling dependency, not evidence that a specific nutrient supplement necessarily increases CAD activity.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"L-Aspartate collection; species, compartment, exposure, co-substrates and manipulation remain explicit.","comparator":null,"unit":null,"notes":"","entity":{"slug":"l-aspartate","display_name":"L-Aspartate","entity_type_key":"small_molecule"}},{"dimension":"plain_language","value_text":"Growth signals can accelerate use of aspartate for nucleotide production.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"Stimulation of de novo pyrimidine synthesis by growth signaling through mTOR and S6K1. · 2013 · https://pubmed.ncbi.nlm.nih.gov/23429703/ · DOI 10.1126/science.1228792","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"fa54325b-1952-57cb-957f-29593bda8d69","evidence_kind":"source_excerpt","locator":"Lines 154-160","start_line":154,"end_line":160,"excerpt":"## l-aspartate-cad-s6k1\nGrowth signals can accelerate use of aspartate for nucleotide production.\nS6K1 directly phosphorylated CAD at Ser1859, connecting mTORC1 signaling to increased de novo pyrimidine synthesis.\nModel: Human HEK293E CAD expression, phosphosite mutation and kinase assays; complementary mouse cell tracing.\nLimitations: This is a signaling dependency, not evidence that a specific nutrient supplement necessarily increases CAD activity.\nEvidence access: Primary full text\nStimulation of de novo pyrimidine synthesis by growth signaling through mTOR and S6K1. · 2013 · https://pubmed.ncbi.nlm.nih.gov/23429703/ · DOI 10.1126/science.1228792","model_system":"Human HEK293E CAD expression, phosphosite mutation and kinase assays; complementary mouse cell tracing.","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":"67970dcb-34e0-5b0a-8c86-d8c3cc183444","stable_key":"import-e37461ea-ea5d-5e2c-8091-138305f6dd70","title":"L-Aspartate: redox transfer, nitrogen partitioning and cross-nutrient mechanisms (2026-09-19)","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":"a2791036b8f554be57d0b40892634bb9c900fa03e7e4c9c95ca08428ed52d614","revision_id":"150613bb-a227-5ec9-9f5c-fb13f5da50c8","review_status":"unverified_draft","notes":""}}],"relations":[],"conflicts":[],"corrections":[],"research":null}