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However, a causal molecular link between ATF6 activation and carcinogenesis is not established. Here, it is found that tumor protein D52 (TPD52) integrates ER stress and UPR signaling with the chaperone machinery by promoting S2P\u2010mediated cleavage of ATF6. Although TPD52 has been generally considered as an oncogene, TPD52 is identified as a novel tumor suppressor in bladder cancer. Significantly, attenuation of the ER stress via depletion of TPD52 facilitated tumorigenesis in a subset of human carcinomas. Furthermore, the APC\n                    <jats:sup>Cdc20<\/jats:sup>\n                    E3 ligase is validated as the upstream regulator marking TPD52 for polyubiquitination\u2010mediated proteolysis. In addition, inactivation of Cdc20 sensitized cancer cells to treatment with the ER stress inducer in a TPD52\u2010dependent manner. Thus, the study suggests that TPD52 is a novel Cdc20 substrate that may modulate ER stress to prevent tumorigenesis.\n                  <\/jats:p>","DOI":"10.1002\/advs.202405441","type":"journal-article","created":{"date-parts":[[2024,10,14]],"date-time":"2024-10-14T16:38:51Z","timestamp":1728923931000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["The Tumor Suppressor TPD52\u2010Governed Endoplasmic Reticulum Stress is Modulated by APC\n                    <sup>Cdc20<\/sup>"],"prefix":"10.1002","volume":"11","author":[{"given":"Weichao","family":"Dan","sequence":"first","affiliation":[{"name":"Department of Urology The First Affiliated Hospital of Xi'an Jiaotong University Xi'an 710061 P. R. China"},{"name":"Key Laboratory for Tumor Precision Medicine of Shaanxi Province The First Affiliated Hospital of Xi'an Jiaotong University Xi'an 710061 P. R. 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