{"id":"c1367516-1423-5cf7-8b06-7f1b6bde39ea","stable_key":"584c58f5-ab9f-53f3-97a9-55783db943b0:tryptophan-trp-mtor","predicate":"depletion_reduces_activity","statement":"IFN-gamma/IDO-driven tryptophan depletion reduced S6K phosphorylation in human HeLa cells; tryptophan repletion restored the mTOR readout.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"context_dependent","is_public":true,"mechanism_event_id":"81ea9a6f-43a5-5dc6-910d-ff29dfe80160","mechanism_event_label":"Local depletion reduced a growth signal as well as changing metabolite supply.","subject":{"id":"9edba4aa-c2f5-5a4e-9750-15e9a38b1822","slug":"ido1","display_name":"Human indoleamine 2,3-dioxygenase 1 / IDO1","entity_type_key":"protein"},"object":{"id":"779b2149-a16f-58b8-815b-7f1f2620da1f","slug":"mtor","display_name":"Human mechanistic target of rapamycin kinase / MTOR","entity_type_key":"protein"},"evidence_count":1,"mechanism_event":{"id":"81ea9a6f-43a5-5dc6-910d-ff29dfe80160","stable_key":"584c58f5-ab9f-53f3-97a9-55783db943b0:tryptophan-trp-mtor-event","event_type":"observed_relationship","label":"Local depletion reduced a growth signal as well as changing metabolite supply.","description":"IFN-gamma/IDO-driven tryptophan depletion reduced S6K phosphorylation in human HeLa cells; tryptophan repletion restored the mTOR readout.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"9edba4aa-c2f5-5a4e-9750-15e9a38b1822","slug":"ido1","display_name":"Human indoleamine 2,3-dioxygenase 1 / IDO1","entity_type_key":"protein"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"779b2149-a16f-58b8-815b-7f1f2620da1f","slug":"mtor","display_name":"Human mechanistic target of rapamycin kinase / MTOR","entity_type_key":"protein"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"769339cb-213b-559e-acc0-07ed00368b94","slug":"l-tryptophan","display_name":"L-Tryptophan","entity_type_key":"small_molecule"},"role":"context_participant","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""},{"entity":{"id":"393e7fb8-8b09-5b6a-b7e4-a31a78b4fcfb","slug":"ifng","display_name":"Human interferon gamma / IFNG","entity_type_key":"cytokine"},"role":"context_participant","stoichiometry":null,"state_label":"","sequence_order":3,"notes":""}]},"contexts":[{"dimension":"availability_state","value_text":"nutrient_deficiency","comparator":null,"unit":null,"notes":"Imported condition classification; unverified.","entity":null},{"dimension":"evidence_access","value_text":"Primary full text, Figure 2","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Human HeLa cells, depleted media and amino-acid add-back.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"S6K phosphorylation is a pathway readout, not direct tryptophan binding to MTOR.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"Tryptophan collection; molecular form, preparation, species, exposure and manipulation remain explicit.","comparator":null,"unit":null,"notes":"","entity":{"slug":"l-tryptophan","display_name":"L-Tryptophan","entity_type_key":"small_molecule"}},{"dimension":"plain_language","value_text":"Local depletion reduced a growth signal as well as changing metabolite supply.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"IDO inhibits a tryptophan sufficiency signal that stimulates mTOR: A novel IDO effector pathway targeted by D-1-methyl-tryptophan. · 2012 · https://pubmed.ncbi.nlm.nih.gov/23264892/ · DOI 10.4161/onci.21716","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"trigger_kind","value_text":"nutrient_deficiency","comparator":null,"unit":null,"notes":"Imported condition classification; unverified.","entity":null}],"evidence":[{"id":"db12b3b2-f13d-5961-8fcb-fc8963213de5","evidence_kind":"source_excerpt","locator":"Lines 402-408","start_line":402,"end_line":408,"excerpt":"## tryptophan-trp-mtor\nLocal depletion reduced a growth signal as well as changing metabolite supply.\nIFN-gamma/IDO-driven tryptophan depletion reduced S6K phosphorylation in human HeLa cells; tryptophan repletion restored the mTOR readout.\nModel: Human HeLa cells, depleted media and amino-acid add-back.\nLimitations: S6K phosphorylation is a pathway readout, not direct tryptophan binding to MTOR.\nEvidence access: Primary full text, Figure 2\nIDO inhibits a tryptophan sufficiency signal that stimulates mTOR: A novel IDO effector pathway targeted by D-1-methyl-tryptophan. · 2012 · https://pubmed.ncbi.nlm.nih.gov/23264892/ · DOI 10.4161/onci.21716","model_system":"Human HeLa cells, depleted media and amino-acid add-back.","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":"73f9d3e7-fdc9-5418-8f3c-f4ef145f6efa","stable_key":"import-584c58f5-ab9f-53f3-97a9-55783db943b0","title":"Tryptophan: transport, protein synthesis, neuroactive metabolites, NAD and microbial pathways (2026-09-19)","document_type":"imported_text","citation_label":"AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text.","file_path":"","sha256":"7dfd20063b91900cb5c6ad675e3e675b7e25ef0fb8304eabac6f263cc5518284","revision_id":"bfafd789-fdf5-521f-bd28-c662e01ec1ea","review_status":"unverified_draft","notes":""}}],"relations":[],"conflicts":[],"corrections":[],"research":null}