{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,18]],"date-time":"2026-10-18T02:50:42Z","timestamp":1792291842589,"version":"4.4.0"},"reference-count":49,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2025,7,20]],"date-time":"2025-07-20T00:00:00Z","timestamp":1752969600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"name":"Graduate Student Research Grant from Shandong Second Medical University","award":["2024YJSCX012"],"award-info":[{"award-number":["2024YJSCX012"]}]},{"name":"Graduate Student Research Grant from Shandong Second Medical University","award":["2023YJSCX014"],"award-info":[{"award-number":["2023YJSCX014"]}]},{"name":"National Natural Science Foundation of Shandong Province","award":["ZR2024QH019"],"award-info":[{"award-number":["ZR2024QH019"]}]},{"name":"Foundation of Weifang Kite Capital Scholars","award":["ydxz2023021"],"award-info":[{"award-number":["ydxz2023021"]}]},{"DOI":"10.13039\/501100018627","name":"Science and Technology Support Plan for Youth Innovation of Colleges and Universities of Shandong Province of China","doi-asserted-by":"publisher","award":["2021KJ107"],"award-info":[{"award-number":["2021KJ107"]}],"id":[{"id":"10.13039\/501100018627","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,9,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Endometriosis is a common estrogen-dependent gynecological disorder characterized by chronic inflammatory responses and frequently associated with clinical infertility. Recent studies have demonstrated that the pathogenesis of this disease is closely linked to dysregulated post-translational modifications. This study focuses on the regulatory role of the ubiquitin\u2013proteasome system (UPS) in endometriosis and, for the first time, reveals the molecular mechanism by which the E3 ubiquitin ligase STIP1 homology and U-box containing protein 1 (CHIP) specifically binds to and ubiquitinates the glycolytic key enzyme 6-phosphofructo-2-kinase\/fructose-2,6-biphosphatase 4 (PFKFB4), thereby promoting its degradation and modulating endometriosis progression. Notably, PFKFB4 is aberrantly overexpressed in ectopic endometrial tissues, with its lysine 305 (K305) residue identified as the critical ubiquitination site mediated by CHIP. Functional studies demonstrate that CHIP-mediated ubiquitination of PFKFB4 significantly suppresses glycolytic activity and inhibits the invasive and migratory capacities of endometriotic cells. More importantly, we provide the first evidence that the PFKFB4 inhibitor 5-(n-(8-methoxy-4-quinolyl) amino) pentyl nitrate (5MPN) exerts potent therapeutic effects in both in vitro and in vivo experimental models of endometriosis. In summary, this study elucidates the crucial regulatory role of CHIP-mediated PFKFB4 ubiquitination in the metabolic reprogramming of endometriosis while also identifying a novel molecular target for developing ubiquitination-targeted therapeutic strategies.<\/jats:p>","DOI":"10.1093\/biolre\/ioaf159","type":"journal-article","created":{"date-parts":[[2025,7,20]],"date-time":"2025-07-20T23:17:22Z","timestamp":1753053442000},"page":"568-580","source":"Crossref","is-referenced-by-count":4,"title":["Ubiquitination of PFKFB4 by CHIP regulates glycolysis and progression in endometriosis"],"prefix":"10.1093","volume":"113","author":[{"given":"Yujie","family":"Tang","sequence":"first","affiliation":[{"name":"Department of Reproductive Medicine, Affiliated Hospital of Shandong Second Medical University , Weifang ,","place":["China"]},{"name":"School of Clinical Medicine, Shandong Second Medical University , Weifang ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ran","family":"Wei","sequence":"additional","affiliation":[{"name":"Department of Reproductive Medicine, Affiliated Hospital of Shandong Second Medical University , Weifang ,","place":["China"]},{"name":"School of Clinical Medicine, Shandong Second Medical University , Weifang ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Runze","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Reproductive Medicine, Affiliated Hospital of Shandong Second Medical University , Weifang ,","place":["China"]},{"name":"School of Clinical Medicine, Shandong Second Medical University , Weifang ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lu","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Reproductive Medicine, Affiliated Hospital of Shandong Second Medical University , Weifang ,","place":["China"]},{"name":"School of Clinical Medicine, Shandong Second Medical University , Weifang ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuemei","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Reproductive Medicine, Affiliated Hospital of Shandong Second Medical University , Weifang ,","place":["China"]},{"name":"School of Clinical Medicine, Shandong Second Medical University , Weifang ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhenhai","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Reproductive Medicine, Affiliated Hospital of Shandong Second Medical University , Weifang ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3274-3701","authenticated-orcid":false,"given":"Chao","family":"Lu","sequence":"additional","affiliation":[{"name":"Department of Reproductive 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