{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:36:58Z","timestamp":1787027818447,"version":"build-2736575974"},"reference-count":69,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2025,1,28]],"date-time":"2025-01-28T00:00:00Z","timestamp":1738022400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000048","name":"NAD: University of Texas at Dallas, American Cancer Society","doi-asserted-by":"publisher","award":["RSG-20-138-01-TBE"],"award-info":[{"award-number":["RSG-20-138-01-TBE"]}],"id":[{"id":"10.13039\/100000048","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000048","name":"NAD: University of Texas at Dallas, American Cancer Society","doi-asserted-by":"publisher","award":["1S10RR025111-01"],"award-info":[{"award-number":["1S10RR025111-01"]}],"id":[{"id":"10.13039\/100000048","id-type":"DOI","asserted-by":"publisher"}]},{"name":"SW, UTHSC San Antonio","award":["RSG-20-138-01-TBE"],"award-info":[{"award-number":["RSG-20-138-01-TBE"]}]},{"name":"SW, UTHSC San Antonio","award":["1S10RR025111-01"],"award-info":[{"award-number":["1S10RR025111-01"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Chronic inflammation is a cancer hallmark and chronic exposure to interleukin-1 (IL-1) transforms castration-sensitive prostate cancer (PCa) cells into more fit castration-insensitive PCa cells. p62 is a scaffold protein that protects cells from nutrient deprivation via autophagy and from cytotoxic reactive oxygen via NF\u03baB and NRF2 antioxidant signaling. Herein, we report that the LNCaP PCa cell line acquires high basal accumulation of the p62-KEAP1 complex when chronically exposed to IL-1. p62 promotes non-canonical NRF2 antioxidant signaling by binding and sequestering KEAP1 to the autophagosome for degradation. But despite high basal p62-KEAP1 accumulation, only two of several NRF2-induced genes analyzed, GCLC and HMOX1, showed high basal mRNA levels, suggesting that the high basal p62-KEAP1 accumulation does not result in overall high basal NRF2 activity. Nutrient starvation induces NRF2-dependent GCLC upregulation and HMOX1 repression, and we found that chronic IL-1-exposed LNCaP cells show hypersensitivity to serum starvation-induced GCLC and HMOX1 regulation. Thus, chronic IL-1 exposure affects cell response to nutrient stress. While HMOX1 expression remains NRF2\/KEAP1-dependent in chronic IL-1-exposed LNCaP cells, GCLC expression is NRF2\/KEAP1-independent. Furthermore, the high basal p62-KEAP1 complex accumulation is not required to regulate GCLC or HMOX1 expression, suggesting cells chronically exposed to IL-1 evolve a novel NRF2-independent role for the p62\/KEAP1 axis.<\/jats:p>","DOI":"10.3390\/cells14030192","type":"journal-article","created":{"date-parts":[[2025,1,28]],"date-time":"2025-01-28T06:47:29Z","timestamp":1738046849000},"page":"192","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Chronic IL-1-Exposed LNCaP Cells Evolve High Basal p62-KEAP1 Complex Accumulation and NRF2\/KEAP1-Dependent and -Independent Hypersensitive Nutrient Deprivation Response"],"prefix":"10.3390","volume":"14","author":[{"given":"Haley","family":"Dahl-Wilkie","sequence":"first","affiliation":[{"name":"Biological Sciences Department, The University of Texas at Dallas, Richardson, TX 75080, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessica","family":"Gomez","sequence":"additional","affiliation":[{"name":"Biological Sciences Department, The University of Texas at Dallas, Richardson, TX 75080, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anastasia","family":"Kelley","sequence":"additional","affiliation":[{"name":"Biological Sciences Department, The University of Texas at Dallas, Richardson, TX 75080, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kirti","family":"Manjit","sequence":"additional","affiliation":[{"name":"Biological Sciences Department, The University of Texas at Dallas, Richardson, TX 75080, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-3581-3422","authenticated-orcid":false,"given":"Basir","family":"Mansoor","sequence":"additional","affiliation":[{"name":"Biological Sciences Department, The University of Texas at Dallas, Richardson, TX 75080, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-6550-7228","authenticated-orcid":false,"given":"Preethi","family":"Kanumuri","sequence":"additional","affiliation":[{"name":"Biological Sciences Department, The University of Texas at Dallas, Richardson, TX 75080, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sammy","family":"Pardo","sequence":"additional","affiliation":[{"name":"Department of Biochemistry & Structural Biology, The University of Texas Health Science Center at San Antonio, San Antonio, TX 78229, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dana","family":"Molleur","sequence":"additional","affiliation":[{"name":"Department of Biochemistry & Structural Biology, The University of Texas Health Science Center at San Antonio, San Antonio, TX 78229, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rafah","family":"Falah","sequence":"additional","affiliation":[{"name":"Biological Sciences Department, The University of Texas at Dallas, Richardson, TX 75080, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anisha R.","family":"Konakalla","sequence":"additional","affiliation":[{"name":"Biological Sciences Department, The University of Texas at Dallas, Richardson, TX 75080, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Morolake","family":"Omiyale","sequence":"additional","affiliation":[{"name":"Biological Sciences Department, The University of Texas at Dallas, Richardson, TX 75080, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susan","family":"Weintraub","sequence":"additional","affiliation":[{"name":"Department of Biochemistry & Structural Biology, The University of Texas Health Science Center at San Antonio, San Antonio, TX 78229, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nikki A.","family":"Delk","sequence":"additional","affiliation":[{"name":"Biological Sciences Department, The University of Texas at Dallas, Richardson, TX 75080, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,1,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"276","DOI":"10.1210\/er.2002-0032","article-title":"Androgen Receptor in Prostate Cancer","volume":"25","author":"Heinlein","year":"2004","journal-title":"Endocr. 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