{"database":"Pride","file_versions":[{"headers":{"Content-Type":["application/json"]},"body":{"files":{"Xlsx":["ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2026/04/PXD059835/FilesCorrespondence.xlsx"],"Txt":["ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2026/04/PXD059835/checksum.txt"],"Raw":["ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2026/04/PXD059835/210521-MClass-21_0844-14-BAZ.raw","ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2026/04/PXD059835/210521-MClass-21_0843-14-BAZ.raw","ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2026/04/PXD059835/210521-MClass-21_0848-14-BAZ.raw","ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2026/04/PXD059835/210521-MClass-21_0845-14-BAZ.raw","ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2026/04/PXD059835/210521-MClass-21_0846-14-BAZ.raw","ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2026/04/PXD059835/210521-MClass-21_0847-14-BAZ.raw"],"Mztab":["ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2026/04/PXD059835/mzTab.mzTab.gz"],"Other":["ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2026/04/PXD059835/txt.zip"]},"type":"primary"},"statusCode":"OK","statusCodeValue":200}],"scores":null,"additional":{"labhead_mail":["pierre.close@uliege.be"],"submitter":["Dominique Baiwir"],"technology_type":["Data-dependent acquisition","Mass Spectrometry","Bottom-up proteomics"],"disease":["Melanoma"],"software":[""],"submitter_keywords":["Protein misfolding","Melanoma","Trna modification"],"full_dataset_link":["https://www.ebi.ac.uk/pride/archive/projects/PXD059835"],"tissue":["B Cell"],"sample_protocol":["Cells were pelleted and washed two times with cold PBS. Pellets were lysed using cytoplasmic buffer solution (340mM sucrose, 3mM of CaCl2, 0.1mMof EDTA, 2mM MgCl2, 1mM DTT, 0.5% NP-40 and protease inhibitor in Tris HCL pH8) and incubated 10min on ice. Lysates were centrifugated at 4°C, 15min at 3500RPM and the supernatant collected were again centrifugated at4°C, 10min at 13.500RPM. Supernatant of this fraction contain cytoplasmic fraction and is store at -80°C. Pellets were washed with wash buffer (Na-phosphate pH6.8, PMSF 1mM, 2% of NP-40 and protease inhibitor in distilled water). After aggregates isolation, pellets were resuspended in 50 mM Tris buffer containing 8M urea, reduced, alkylated and digested using Lys-C/Trypsin mix (Promega) for 4 hours at 37°C then the urea concentration was lowered to 1M by dilution with Tris buffer and digested overnight. The digestion was stopped by adding trifluoroacetic acid and the half of the protein digests was purified using Pierce C18 Tip 10µL bed (Thermo Scientific) and dried. Peptides were suspended in 0.1% TFA and spiked with a commercial mixture of protein digest standards originated from non-human biological material: the MassPREP™ Digestion Standards (Waters), at 50 fmol of ADH per injection. This commercial standard consists of two standard mixtures (MPDS Mix 1 and MPDS Mix 2) containing protein digests of Yeast Alcohol Dehydrogenase (ADH), Rabbit Glycogen Phosphorylase b, Bovine Serum Albumin, and Yeast Enolase present at known protein ratio; allowing therefore to check for relative quantitation of the samples spiked. Peptides were independently analyzed by LC-ESI-MS/MS on an Acquity M-Class UPLC (Waters) hyphenated to a Q Exactive Plus (Thermo Scientific), in nanoelectrospray positive ion mode. The trap and analytical columns were respectively Symmetry C18 5µm (180µmx20mm) and HSS T3 C18 1.8µm (75µmx250mm) (both Waters). The samples were loaded at 20µL/min on the trap column in 98/2 water 0.1% formic acid (A)/acetonitrile 0.1% formic acid (B) during 3 minutes and subsequently separated on the analytical column at a flow rate of 600 nL/min with a linear gradient of 150 minutes long (0 min, 98/2 A/B v/v; 5 min, 93/7; 135 min, 70/30; 150 min, 60/40). The total run time was 180 min. TopN-MSMS method where N was set to 12 was employed with resolution of 70000 in MS, AGC target of 1e6 or Maximum injection time of 50 ms and a mass range from 400 to 1600 m/z. The parameters for MS2 spectrum acquisition were, resolution of 17500 with AGC target of 1e5 or Maximum injection time of 50 ms and isolation Window of 2.0 m/z with collision energy (NCE) of 28."],"repository":["Pride"],"quantification_method":[""],"modification":[""],"data_protocol":["MaxQuant v 1.6.17.0 was used to perform peptides and proteins identification against SwissProt database limited to Mus Musculus taxonomy (17038 sequences, June 2020) and relative quantification using LFQ normalization [J. Cox, M.Y. Hein, C.A. Luber, I. Paron, N. Nagaraj, M. Mann, Mol. Cell. Proteomics: MCP, 13 (2014), pp. 2513–2526]. Oxidation of methionines and deamidation of glutamine and asparagine were set as variable modifications, carbamidomethylation of the cysteines as fixed modification, peptide spectrum match (PSM) and protein false discovery rates (FDR) were both set at 0.01."],"omics_type":["Proteomics"],"labhead":["Pierre Close"],"instrument_platform":[""],"labhead_affiliation":["Lab of Cancer Signaling, GIGA-Institute, ULiege, Belgium"],"submission_type":["COMPLETE"],"species":["Mus Musculus (mouse)"],"publication":["41735308 Dziagwa C, Seca C, Capron C, Maurizy C, An N, Heusdens D, Budden T, Martin-Morales L, Susaeta Ruiz M, Renaude E, El-Hachem N, Vanleyssem R, Leclercq M, Blomme A, Chariot A, Utikal J, Viros A, Rapino F, Delaunay S, Close P. Disruption of tRNA threonylation triggers RIG-I mediated anti-tumour immune response. Nat Commun. 2026 17(1):3145 10.1038/s41467-026-69964-2"],"submitter_mail":["d.baiwir@ulg.ac.be"],"submitter_affiliation":["University of Liege"],"submitter_country":["Belgium"],"doi":["10.6019/PXD059835"],"pubmed_abstract":["Tumour-induced mechanisms of immune evasion hinder immune response to cancer, particularly in melanoma. mRNA translation, by ensuring accurate protein synthesis, regulates cancer phenotypes and immune response, but the underlying mechanisms remain unclear. Here, we reveal how O-sialoglycoprotein endopeptidase (OSGEP), catalysing the tRNA modification N<sup>6</sup>-threonylcarbamoyladenosine (t<sup>6</sup>A), drives protein homeostasis in cancer cells to maintain T-cell exclusion and prevent anti-tumour immune response. t<sup>6</sup>A-deficient melanoma cells disrupt efficient cytoplasmic translation of ANN codons (trinucleotides with A in the first position and N = any nucleotide), causing specific protein aggregation and the formation of integrated stress response-dependent stress granules. We discovered that OSGEP loss triggers melanoma regression by relocating RIG-I to stress granules, leading to its pathway activation. As a result, T-cells are recruited to the tumour site and orchestrate an anti-tumour immune response. Finally, an OSGEP-driven gene signature in melanoma patients is associated with T-cell infiltration and improved overall survival. Together, our findings position t<sup>6</sup>A tRNA modification as a promising therapeutic target for melanoma treatment."],"pubmed_title":["Disruption of tRNA threonylation triggers RIG-I mediated anti-tumour immune response."],"pubmed_authors":["Dziagwa Cléa C, Seca Christian C, Capron Coralie C, Maurizy Chloe C, An Ning N, Heusdens Denis D, Budden Timothy T, Martin-Morales Lorena L, Susaeta Ruiz Miguel M, Renaude Elodie E, El-Hachem Najla N, Vanleyssem Raphael R, Leclercq Marine M, Blomme Arnaud A, Chariot Alain A, Utikal Jochen J, Viros Amaya A, Rapino Francesca F, Delaunay Sylvain S, Close Pierre P"],"additional_accession":[]},"is_claimable":false,"name":"LC-M/MS Protein aggregation isolation is murine melanoma lines after OSGEP depletion","description":"The immune response in cancer, particularly in melanoma, is often hindered by tumour-induced immune evasion strategies, but the precise mechanisms for this remains unclear. Here, we reveal how the tRNA modification threonine-6-adenosine (t6A), mediated by O-sialoglycoprotein endopeptidase (OSGEP), maintains proteostasis in melanoma cells to prevent anti-tumour immune recognition. Cytoplasmic translation depends on the formation of t6A modification in position 37 of tRNANNU for efficient decoding of ANN codons. Defective protein homeostasis resulting from knockdown of OSGEP triggers accumulation of protein aggregates and the formation of stress granules. This disrupted codon-specific translation induces the activation of RIG-I and type I interferon response. Hence, t6A-deficient tumours prompt recruitment and activation of T-cells, affecting tumour growth. Finally, an OSGEP-driven gene signature in melanoma patients is predictive for T-cell infiltration and overall survival. Together, our results reveal t6A tRNA modification as a novel therapeutic target to fight melanoma.","dates":{"publication":"2026-04-06","submission":"2025-01-15"},"accession":"PXD059835","cross_references":{"TAXONOMY":["NEWT:330879","NEWT:377960","NEWT:1131","NEWT:35795","NEWT:2042546","NEWT:259447","NEWT:295546","NCBITaxon:2719036","NEWT:1334565","NEWT:625351","NEWT:258594","NCBITaxon:1280","NEWT:112503","NEWT:1129","NEWT:309807","NEWT:59753","NEWT:89184","NEWT:309800","NEWT:281395","NEWT:247480","NEWT:1211601","NEWT:876138","NEWT:44271","NEWT:193516","NEWT:2315688","NEWT:592321","NEWT:1073882","NEWT:6819","NEWT:475174","NEWT:1599","NEWT:428386","NEWT:1117","NEWT:498257","NEWT:10036","NEWT:32264","NEWT:12215","NEWT:1590","NEWT:10034","NEWT:33114","NEWT:1596","NEWT:661410","NEWT:638632","NEWT:224326","NEWT:294671","NEWT:376619","NEWT:1748418","NCBITaxon:79857","NEWT:1096976","NEWT:3765","NEWT:3767","NEWT:1589","NEWT:135622","NEWT:4615","NEWT:672127","NEWT:35786","NEWT:1580","NEWT:399784","NEWT:96731","NEWT:656064","NEWT:1582","NEWT:3760","NEWT:1584","NEWT:2086595","NEWT:36630","NEWT:1585","NEWT:383379","NEWT:381198","NEWT:418106","NCBITaxon:12721","NEWT:10029","NEWT:913645","NEWT:2492962","NEWT:641809","NEWT:1392488","NEWT:38815","NEWT:317447","NEWT:4688","NEWT:3357","NEWT:7719","NEWT:29073","NEWT:5530","NEWT:868565","NEWT:135674","NEWT:1562698","NEWT:79329","NEWT:30069","NEWT:12637","NEWT:59729","NEWT:2164133","NEWT:295105","NEWT:108061","NEWT:60711","NEWT:2020713","NEWT:224308","NEWT:3347","NEWT:49928","NEWT:3349","NEWT:160621","NEWT:2502409","NEWT:212790","NEWT:110368","NEWT:1916073","NEWT:1310161","NEWT:77133","NEWT:145481","NEWT:1310165","NEWT:29058","NCBITaxon:79824","NEWT:410658","NEWT:5516","NEWT:44688","NEWT:44689","NEWT:370038","NEWT:498211","NEWT:345076","NEWT:347256","NEWT:5518","NEWT:398007","NEWT:1527468","NEWT:498217","NEWT:498216","NEWT:11320","NEWT:246196","NEWT:246197","NEWT:145458","NEWT:1310173","NEWT:200795","NEWT:2579791","NEWT:44685","NEWT:161934","NEWT:156587","NEWT:1148","NEWT:5508","NEWT:3329","NEWT:419481","NEWT:5507","NEWT:260499","NEWT:410661","NEWT:329854","NEWT:1140","NCBITaxon:2157","NEWT:2066563","NEWT:2649329","NEWT:1143","NEWT:1287689","NEWT:1094343","NEWT:1462472","NEWT:1336795","NEWT:644042","NEWT:150808","NEWT:1182590","NEWT:3712","NEWT:3711","NEWT:3714","NCBITaxon:37162","NEWT:270643","NEWT:3715","NEWT:1538","NEWT:2065263","NEWT:199225","NEWT:177437","NEWT:717966","NEWT:10891","NEWT:10418","NEWT:118698","NEWT:1616117","NEWT:118696","NEWT:34865","NEWT:52283","NEWT:28174","NEWT:284812","NEWT:8175","NEWT:43330","NEWT:1603293","NEWT:44664","NEWT:43346","NEWT:3702","NEWT:1245466","NEWT:3704","NEWT:244366","NEWT:1246791","NEWT:176597","NEWT:118694","NEWT:2850","NEWT:118691","NEWT:34871","NEWT:9006","NEWT:33548","NEWT:52299","NEWT:8165","NEWT:96794","NEWT:10886","NEWT:3708","NEWT:332648","NEWT:44670","NEWT:926571","NEWT:536231","NEWT:376219","NEWT:219813","NEWT:1510","NEWT:460519","NEWT:1515","NEWT:572307","NEWT:1432138","NEWT:2714896","NEWT:1424507","NEWT:1194599","NEWT:272844","NEWT:1348799","NEWT:1608994","NEWT:33995","NEWT:55784","NEWT:1303443","NEWT:9483","NEWT:485","NEWT:56636","NEWT:2499525","NEWT:1122981","NEWT:2853422","NEWT:1122984","NEWT:487","NEWT:1538553","NEWT:1679718","NEWT:480","NEWT:67767","NEWT:45972","NEWT:46835","NEWT:109757","NEWT:582580","NEWT:1185650","NEWT:216778","NEWT:1502","NEWT:128017","NEWT:2836","NEWT:376686","NEWT:237610","NEWT:95486","EFO:0001352","NEWT:119562","NEWT:1883446","NEWT:31345","NEWT:1233435","NEWT:118223","NEWT:11757","NEWT:987059","NEWT:109760","NEWT:29031","NEWT:317047","NEWT:1509","NEWT:491","NEWT:460523","NEWT:45954","NEWT:235443","NEWT:1579","NEWT:1757312","NEWT:85694","NEWT:109786","NEWT:1922344","NEWT:108458","NEWT:5936","NEWT:85692","NEWT:321967","NEWT:320637","NEWT:1078283","NEWT:3750","NEWT:983964","NEWT:11706","NEWT:32644","NEWT:527796","NEWT:279010","NEWT:499175","NEWT:109779","NEWT:3745","NEWT:1715989","NCBITaxon:4751","NEWT:3747","NEWT:1116234","NEWT:415978","NEWT:1255228","NEWT:410289","NEWT:191701","NEWT:373153","NEWT:1640278","NEWT:9054","NEWT:472","NEWT:940825","NEWT:29459","NEWT:529507","NEWT:1071661","NEWT:1380096","NEWT:28128","NEWT:470","NEWT:41122","NEWT:5911","NEWT:1328300","NEWT:748693","NCBITaxon:50557","NEWT:39251","NEWT:29491","NEWT:101841","NEWT:446","NEWT:153481","NEWT:2014887","NEWT:33952","NEWT:11723","NEWT:445","NEWT:153009","NEWT:261756","NEWT:166314","NEWT:166313","NEWT:63366","NEWT:63367","NEWT:29488","NEWT:215402","NEWT:1547","NEWT:1290454","NEWT:3726","NEWT:906914","NEWT:81231006","NEWT:30455","NEWT:28141","NEWT:9031","NEWT:27292","NEWT:1050722","NEWT:3728","NEWT:108931","NEWT:1293497","NEWT:1055524","NEWT:548","NEWT:150475","NEWT:267872","NEWT:381666","NEWT:172269","NEWT:9534","NEWT:2126348","NEWT:5180","NEWT:256737","NEWT:299467","NEWT:9541","NEWT:51350","NEWT:8694","NEWT:33936","NEWT:8692","NEWT:542","NEWT:2903","NEWT:185579","NEWT:872227","NEWT:13076","NEWT:2587410","NEWT:207340","NEWT:1006581","NEWT:8673","NEWT:33940","NEWT:2126337","NEWT:550","NEWT:253237","NEWT:10804","NEWT:3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