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It is largely unknown whether disulfide bond formation of PDIA1 substrates is driven by one or both CGHC motifs. Using active\u2010site trapping mutants in prostate cancer cells combined with mass spectrometry, we identified 29 proteins uniquely bound to the C\n                    <jats:sub>53<\/jats:sub>\n                    GHC\n                    <jats:sub>56<\/jats:sub>\n                    domain and 20 proteins uniquely bound to the C\n                    <jats:sub>397<\/jats:sub>\n                    GHC\n                    <jats:sub>400<\/jats:sub>\n                    domain. Hyaluronan\u2010mediated motility receptor (HMMR) was validated as a PDIA1 C\n                    <jats:sub>397<\/jats:sub>\n                    GHC\n                    <jats:sub>400<\/jats:sub>\n                    \u2010specific substrate, with PDIA1 catalysing disulfide bond formation between Cys242 and Cys293. PDIA1 knockdown induced HMMR ubiquitination, blocked androgen receptor nuclear translocation, and suppressed prostate cancer cell growth, survival, and migration. These findings reveal a previously unknown role of PDIA1 in prostate cancer biology.\n                  <\/jats:p>","DOI":"10.1002\/1873-3468.70377","type":"journal-article","created":{"date-parts":[[2026,6,15]],"date-time":"2026-06-15T07:17:57Z","timestamp":1781507877000},"page":"1897-1910","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["<scp>PDIA1<\/scp>\n                    promotes androgen receptor activation and prostate cancer cell survival through enhancing\n                    <scp>HMMR<\/scp>\n                    stability"],"prefix":"10.1002","volume":"600","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-3588-1900","authenticated-orcid":false,"given":"Sishu","family":"Yu","sequence":"first","affiliation":[{"name":"School of Biology and Biological Engineering, South China University of Technology, University Town  Guangzhou China"},{"name":"Guangdong Engineering Research Center of Low\u2010Carbon 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