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However, the protein interactome of TDP\u201043 remains incompletely defined. In this study, we aimed to identify putative TDP\u201043 protein partners within the nucleus and the cytoplasm and with different disease models of TDP\u201043 by comparing TDP\u201043 interaction partners in three different cell lines. We verified the levels of interaction of protein partners under stress conditions as well as after introducing TDP\u201043 variants containing ALS missense mutations (G294V and A315T). Overall, we identified 58 putative wild\u2010type TDP\u201043 interactors, including novel binding partners responsible for RNA metabolism and splicing. Oxidative stress exposure broadly led to changes in TDP\u201043\n                    <jats:sup>WT<\/jats:sup>\n                    interactions with proteins involved in mRNA metabolism, suggesting a dysregulation of the transcriptional machinery early in disease. Conversely, although G294V and A315T mutations are both located in the C\u2010terminal domain of TDP\u201043, both mutants presented different interactome profiles with most interaction partners involved in translational and transcriptional machinery. Overall, by correlating different cell lines and disease\u2010simulating interventions, we provide a list of high\u2010confidence TDP\u201043 interaction partners, including novel and previously reported proteins. Understanding pathological changes to TDP\u201043 and its specific interaction partners in different models of stress is critical to better understand TDP\u201043 proteinopathies and provide novel potential therapeutic targets and biomarkers.\n                    <jats:boxed-text content-type=\"graphic\" position=\"anchor\">\n                      <jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/jnc70079-fig-0008-m.png\">\n                        <jats:alt-text>image<\/jats:alt-text>\n                      <\/jats:graphic>\n                    <\/jats:boxed-text>\n                  <\/jats:p>","DOI":"10.1111\/jnc.70079","type":"journal-article","created":{"date-parts":[[2025,5,14]],"date-time":"2025-05-14T06:01:14Z","timestamp":1747202474000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Proteomics 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