{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,27]],"date-time":"2026-06-27T04:48:29Z","timestamp":1782535709316,"version":"3.54.5"},"reference-count":64,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2026,6,22]],"date-time":"2026-06-22T00:00:00Z","timestamp":1782086400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100021171","name":"GuangDong Basic and Applied Basic Research Foundation","doi-asserted-by":"crossref","award":["#2024A1515010342"],"award-info":[{"award-number":["#2024A1515010342"]}],"id":[{"id":"10.13039\/501100021171","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antioxidants"],"abstract":"<jats:p>SQSTM1\/p62 is a multifunctional scaffold protein that plays important roles in selective autophagy and cellular redox homeostasis. While phosphorylation-dependent regulation of p62 has been extensively studied, the functional significance of oxidative modification remains incompletely understood. Our previous studies showed that the natural small compound Alternol induces cancer cell-specific killing via a xanthine oxidase-mediated strong oxidative stress. In this study, we investigated p62-associated oxidative responses under Alternol-induced oxidative stress conditions in prostate cancer cells. Using biochemical assays and cell-based models, we found that Alternol treatment was associated with the accumulation of oxidized and high-molecular-weight p62 species, accompanied by altered KEAP1 association and increased Nrf2-associated signaling. Furthermore, Alternol-induced p62 oxidative modification was associated with autophagy-related responses and adaptive cellular survival under oxidative stress conditions. Disruption of the Cys105\/113-dependent oxidative modification response attenuated Nrf2-associated transcriptional activity and increased cellular sensitivity to Alternol treatment. Collectively, our findings support an association between p62 oxidative modification and redox-responsive autophagy- and antioxidant-associated signaling pathways under Alternol-induced oxidative stress conditions, providing new insight into adaptive stress responses in prostate cancer cells.<\/jats:p>","DOI":"10.3390\/antiox15060779","type":"journal-article","created":{"date-parts":[[2026,6,26]],"date-time":"2026-06-26T05:52:11Z","timestamp":1782453131000},"page":"779","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Alternol-Induced Oxidative Modification of SQSTM1\/p62 Is Associated with Nrf2 Signaling and Autophagy-Related Responses in Prostate Cancer Cells"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-9698-9599","authenticated-orcid":false,"given":"Wang","family":"Liu","sequence":"first","affiliation":[{"name":"Department of Urology, The University of Kansas Medical Center, Kansas City, KS 66160, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiang","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Urology, The Affiliated Hospital of Guangdong Medical University, Zhanjiang 524001, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5872-6443","authenticated-orcid":false,"given":"Changlin","family":"Li","sequence":"additional","affiliation":[{"name":"Tianjin Institute of Urology, The Second Hospital of Tianjin Medical University, Tianjin 300211, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haixia","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Urology, The University of Kansas Medical Center, Kansas City, KS 66160, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-6368-5215","authenticated-orcid":false,"given":"Ruibao","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Urology, The University of Kansas Medical Center, Kansas City, KS 66160, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xing","family":"Zeng","sequence":"additional","affiliation":[{"name":"Department of Urology, The University of Kansas Medical Center, Kansas City, KS 66160, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Urology, The University of Kansas Medical Center, Kansas City, KS 66160, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8777-082X","authenticated-orcid":false,"given":"Cuncong","family":"Zhong","sequence":"additional","affiliation":[{"name":"Department of Electrical Engineering and Computer Science, The University of Kansas, Lawrence, KS 66045, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiangwei","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Urology, The Affiliated Hospital of Guangdong Medical University, Zhanjiang 524001, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6242-5117","authenticated-orcid":false,"given":"Benyi","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Urology, The University of Kansas Medical Center, Kansas City, KS 66160, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,6,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1186\/s11658-016-0031-z","article-title":"p62 links the autophagy pathway and the ubiqutin-proteasome system upon ubiquitinated protein degradation","volume":"21","author":"Liu","year":"2016","journal-title":"Cell. 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