{"id":"2860a905-7230-5f5a-8de3-38bb36b52e45","stable_key":"584c58f5-ab9f-53f3-97a9-55783db943b0:tryptophan-w-to-f-shortage","predicate":"supports_shortage_associated_substitution","statement":"Under IFN-gamma/IDO1-associated tryptophan shortage, human cancer cells continued translation with WARS1-associated phenylalanine incorporation at tryptophan positions.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"context_dependent","is_public":true,"mechanism_event_id":"e6e102a1-cb46-5e40-829a-9fe82ce75a56","mechanism_event_label":"Severe local shortage can change what a cancer cell puts into a protein.","subject":{"id":"d14146bc-16c2-5f9e-98fb-6813f0a0210c","slug":"wars1","display_name":"Human cytosolic tryptophanyl-tRNA synthetase / WARS1","entity_type_key":"protein"},"object":{"id":"874e0ce7-43d1-51b0-9411-4c3d0d08fab0","slug":"human-cancer-w-to-f-substitution","display_name":"Human cancer-cell tryptophan-to-phenylalanine translational substitution","entity_type_key":"cellular_process"},"evidence_count":1,"mechanism_event":{"id":"e6e102a1-cb46-5e40-829a-9fe82ce75a56","stable_key":"584c58f5-ab9f-53f3-97a9-55783db943b0:tryptophan-w-to-f-shortage-event","event_type":"observed_relationship","label":"Severe local shortage can change what a cancer cell puts into a protein.","description":"Under IFN-gamma/IDO1-associated tryptophan shortage, human cancer cells continued translation with WARS1-associated phenylalanine incorporation at tryptophan positions.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"d14146bc-16c2-5f9e-98fb-6813f0a0210c","slug":"wars1","display_name":"Human cytosolic tryptophanyl-tRNA synthetase / WARS1","entity_type_key":"protein"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"874e0ce7-43d1-51b0-9411-4c3d0d08fab0","slug":"human-cancer-w-to-f-substitution","display_name":"Human cancer-cell tryptophan-to-phenylalanine translational substitution","entity_type_key":"cellular_process"},"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":"9edba4aa-c2f5-5a4e-9750-15e9a38b1822","slug":"ido1","display_name":"Human indoleamine 2,3-dioxygenase 1 / IDO1","entity_type_key":"protein"},"role":"context_participant","stoichiometry":null,"state_label":"","sequence_order":3,"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":4,"notes":""},{"entity":{"id":"190407ad-0219-54b5-b05f-7c75f3895ca6","slug":"l-phenylalanine","display_name":"L-Phenylalanine","entity_type_key":"small_molecule"},"role":"context_participant","stoichiometry":null,"state_label":"","sequence_order":5,"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 abstract; primary correction full text reviewed","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Human cancer-cell depletion, molecular assays and tumor proteomics.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Not a DNA mutation or a universal consequence of a low-tryptophan meal. Tumor proteomic filtering was clarified in a correction. Correction record: The 2022 author correction adds omitted funding acknowledgements and clarifies that the maximum-sample peptide filter was used in the intra-tumour analysis (Fig. 3f) but not for W>F substitutants in the tumour-specific analysis (Fig. 3a). Authors report similar biological conclusions with both strategies. This is a publication correction, not an opposing mechanism claim. https://www.nature.com/articles/s41586-022-05097-y","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":"Severe local shortage can change what a cancer cell puts into a protein.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"Tryptophan depletion results in tryptophan-to-phenylalanine substitutants. · 2022 · https://pubmed.ncbi.nlm.nih.gov/35264796/ · DOI 10.1038/s41586-022-04499-2","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":"c33b7e0f-91ce-54c3-b43c-2cda8ad26c0e","evidence_kind":"source_excerpt","locator":"Lines 122-128","start_line":122,"end_line":128,"excerpt":"## tryptophan-w-to-f-shortage\nSevere local shortage can change what a cancer cell puts into a protein.\nUnder IFN-gamma/IDO1-associated tryptophan shortage, human cancer cells continued translation with WARS1-associated phenylalanine incorporation at tryptophan positions.\nModel: Human cancer-cell depletion, molecular assays and tumor proteomics.\nLimitations: Not a DNA mutation or a universal consequence of a low-tryptophan meal. Tumor proteomic filtering was clarified in a correction. Correction record: The 2022 author correction adds omitted funding acknowledgements and clarifies that the maximum-sample peptide filter was used in the intra-tumour analysis (Fig. 3f) but not for W>F substitutants in the tumour-specific analysis (Fig. 3a). Authors report similar biological conclusions with both strategies. This is a publication correction, not an opposing mechanism claim. https://www.nature.com/articles/s41586-022-05097-y\nEvidence access: Primary abstract; primary correction full text reviewed\nTryptophan depletion results in tryptophan-to-phenylalanine substitutants. · 2022 · https://pubmed.ncbi.nlm.nih.gov/35264796/ · DOI 10.1038/s41586-022-04499-2","model_system":"Human cancer-cell depletion, molecular assays and tumor proteomics.","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. 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