ArticleMolecular cell2024
Arginine deprivation enriches lung cancer proteomes with cysteine by inducing arginine-to-cysteine substitutants.
Article in Molecular cell, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed.
- Metabolic immune checkpoints (MICs) in cancer: from molecular mechanisms to challenges and opportunities in clinical translation.Signal transduction and targeted therapy · 2026Review
- Mapping the functional dark proteome in cancer.Nature reviews. Cancer · 2026Review
- Global and specific mechanisms stimulate mistranslation in cancer.Nature cell biology · 2026Article
- Review
- A high-resolution circulating metabolic atlas of lung adenocarcinoma progression supports early and accurate diagnosis.Cell reports. Medicine · 2026Article
- Column switching liquid chromatography dual mass spectrometry system for simultaneous untargeted metabolomics and targeted exposomics.Nature communications · 2026Article
- Arginine Deprivation of ASS1-Deficient Cancers Drives Mistranslation and Shared Neoepitope Production.Cancer research · 2026Article
- Human aminoacyl-tRNA synthetases as integrators of translation and cell signalling networks.Nature reviews. Molecular cell biology · 2026Review
- Histidine to glutamine substitutants, a regulated process that impacts cell survival and suggests histidine shortage in cancer.Cell death discovery · 2026Article
- Metabolic reprogramming in cancer: dysregulation of glucose, lipid, and amino acid pathways and therapeutic opportunities.Molecular biomedicine · 2026Review
- Clinical development of cancer vaccines.Nature medicine · 2026Review
- Ribosome-associated quality control of aberrant protein production during amino acid limitation.bioRxiv : the preprint server for biology · 2026Article
- Non-canonical and induced neoantigens as emerging sources of cancer-specific immunotherapy targets.Frontiers in immunology · 2026Review
- A microenvironment-driven HLA-II-associated insulin neoantigen elicits persistent memory T cell activation in diabetes.Nature immunology · 2026Article
- Molecular mechanisms and therapies for tumor inhibition through the arginine metabolism pathway.Frontiers in oncology · 2026Review
- The Multi-dimensional Mechanisms and Transformation Prospects of the Intratumoral Microbiota-Arginine Metabolism Axis in Tumor Progression and Immune Regulation.International journal of medical sciences · 2026Review
- Endothelial Arginine Metabolism in Angiogenesis: Mechanistic Insights from Tissue Repair to Tumor Progression.Metabolites · 2025Review
- Alternate RNA decoding results in stable and abundant proteins in mammals.bioRxiv : the preprint server for biology · 2025Article
- Arginine Metabolic Disruption Impairs Hair Regeneration via ROS-Mediated Inactivation of mTOR Signaling in Androgenetic Alopecia.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Targeting AQP5-mediated arginine deprivation in gastric cancer stem cells restores NK cell anti-tumor immunity.Cell reports. Medicine · 2025Article
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Authors and funding
10 authors.
Funding
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Abstract
Many types of human cancers suppress the expression of argininosuccinate synthase 1 (ASS1), a rate-limiting enzyme for arginine production. Although dependency on exogenous arginine can be harnessed by arginine-deprivation therapies, the impact of ASS1 suppression on the quality of the tumor proteome is unknown. We therefore interrogated proteomes of cancer patients for arginine codon reassignments (substitutants) and surprisingly identified a strong enrichment for cysteine (R>C) in lung tumors specifically. Most R>C events did not coincide with genetically encoded R>C mutations but were likely products of tRNA misalignments. The expression of R>C substitutants was highly associated with oncogenic kelch-like epichlorohydrin (ECH)-associated protein 1 (KEAP1)-pathway mutations and suppressed by intact-KEAP1 in KEAP1-mutated cancer cells. Finally, functional interrogation indicated a key role for R>C substitutants in cell survival to cisplatin, suggesting that regulatory codon reassignments endow cancer cells with more resilience to stress. Thus, we present a mechanism for enriching lung cancer proteomes with cysteines that may affect therapeutic decisions.
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