{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T20:28:51Z","timestamp":1786566531720,"version":"build-2736575974"},"reference-count":20,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2026,4,6]],"date-time":"2026-04-06T00:00:00Z","timestamp":1775433600000},"content-version":"vor","delay-in-days":5,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T00:00:00Z","timestamp":1775001600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100007129","name":"Natural Science Foundation of Shandong Province","doi-asserted-by":"publisher","award":["ZR2022MC125"],"award-info":[{"award-number":["ZR2022MC125"]}],"id":[{"id":"10.13039\/501100007129","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J Biochem &amp;amp; Molecular Tox"],"published-print":{"date-parts":[[2026,4]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Tumor necrosis factor receptor\u2010associated factor interacting protein (TRAIP) has emerged as a critical regulator of multiple oncogenic processes across various malignancies. However, its specific functional role and underlying mechanisms in breast cancer pathogenesis remain to be fully elucidated. Integrated bioinformatics analysis of TCGA and GTEx datasets was performed to assess TRAIP expression patterns. Complementary experimental validation was conducted using immunohistochemistry, qRT\u2010PCR, and western blot in clinical specimens. Functional characterization of TRAIP in breast cancer cells was achieved through CCK\u20108 proliferation assays, colony formation analysis, transwell migration\/invasion tests, wound healing experiments, and flow cytometric apoptosis detection. Mechanistic investigations employed co\u2010immunoprecipitation and ubiquitination assays to delineate the TRAIP\u2010PLSCR4 interaction, supplemented by rescue experiments to confirm functional interdependence. Consistent overexpression of TRAIP was observed in breast cancer tissues compared to normal controls. Genetic knockdown of TRAIP significantly attenuated malignant phenotypes, including: (1) reduction in cellular proliferation, (2) decrease in colony\u2010forming capacity, (3) reduction in migratory\/invasive potential, and (4) increase in apoptosis rates (Annexin V staining). Mechanistically, TRAIP functioned as an E3 ubiquitin ligase mediating proteasomal degradation of PLSCR4 through K48\u2010linked polyubiquitination (co\u2010IP validation). Notably, PLSCR4 silencing effectively rescued the tumor\u2010suppressive effects of TRAIP knockdown. This study identifies a novel TRAIP\/PLSCR4 regulatory axis in breast cancer pathogenesis, wherein TRAIP exerts its oncogenic function via ubiquitination\u2010dependent degradation of tumor\u2010suppressive PLSCR4. These findings position TRAIP as a promising therapeutic target for precision breast cancer interventions.<\/jats:p>","DOI":"10.1002\/jbt.70825","type":"journal-article","created":{"date-parts":[[2026,4,7]],"date-time":"2026-04-07T03:19:37Z","timestamp":1775531977000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Loss of TRAIP Could Attenuate the Breast Cancer Cells Development by Regulating PLSCR4 Stabilization"],"prefix":"10.1002","volume":"40","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-3535-3008","authenticated-orcid":false,"given":"Zhiqiang","family":"Dong","sequence":"first","affiliation":[{"name":"Science and Technology Innovation Center Shandong First Medical University &amp; Shandong Academy of Medical Sciences Jinan Shandong China"},{"name":"Institute of Basic Research in Clinical Medicine China Academy of Chinese Medical Sciences Beijing China"},{"name":"Health College Yantai Nanshan University Yantai Shandong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiaoyun","family":"Chen","sequence":"additional","affiliation":[{"name":"Science and Technology Innovation Center Shandong First Medical University &amp; 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