{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,10]],"date-time":"2026-08-10T21:12:55Z","timestamp":1786396375353,"version":"build-2736575974"},"reference-count":33,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2025,10,22]],"date-time":"2025-10-22T00:00:00Z","timestamp":1761091200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2025,10,22]],"date-time":"2025-10-22T00:00:00Z","timestamp":1761091200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["82304018"],"award-info":[{"award-number":["82304018"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["82230105"],"award-info":[{"award-number":["82230105"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["82373471"],"award-info":[{"award-number":["82373471"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Cell Commun Signal"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>The pathogenesis of psoriasis is characterized by dysregulated post-translational modifications, with particular emphasis on fucosylation\u2014a glycosylation process mediated by fucosyltransferases (FUTs). Keratin 17 (K17), overexpressed in psoriatic keratinocytes, drives inflammation and proliferation, but its interplay with fucosylation remains unclear. This study aimed to elucidate the role of fucosylation in psoriasis, specifically focusing on the regulation of K17 stability by FUT11.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>To investigate fucosylation dynamics, we employed single-cell RNA sequencing (scRNA-seq) to analyze N-glycan biosynthesis activity in psoriatic versus healthy keratinocytes. Fucosylation levels were assessed in human and murine psoriatic lesions, as well as in cytokine-stimulated keratinocytes, using Aleuria aurantia lectin (AAL). An imiquimod (IMQ)-induced psoriasis-like mouse model and primary keratinocytes treated with psoriasis-associated cytokines (Pso-Mix) (IL-17, TNF-\u03b1, IL-1\u03b1, OSM and IL-22) were utilized to evaluate the effects of 2-fluorofucose (2-FF) and FUT11 siRNA. We further explored the mechanisms regulating K17 stability through immunoprecipitation, ubiquitination assays, and cycloheximide chase experiments.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Our findings revealed that psoriatic keratinocytes exhibited elevated levels of fucosylation, which correlated with upregulation of FUT11. Administration of 2-FF or silencing FUT11 significantly attenuated IMQ-induced inflammation, as evidenced by reductions in epidermal thickness, immune cell infiltration, and the expression of pro-inflammatory mediators such as IL-17A and CCL20. We demonstrated that FUT11 mediates \u03b1-1,3-fucosylation of K17, stabilizing it through K63-linked ubiquitination facilitated. Notably, silencing FUT11 disrupted the interaction between ubiquitination and fucosylation, leading to accelerated K17 degradation and a subsequent decrease in keratinocyte proliferation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Our results indicate that FUT11-driven fucosylation is integral to the stabilization of K17 via K63 ubiquitination, thereby perpetuating psoriatic inflammation. Targeting FUT11 or inhibiting fucosylation with 2-FF presents a novel therapeutic strategy for psoriasis management. This study highlights the critical interplay between glycosylation and ubiquitination in the pathophysiology of psoriasis, positioning FUT11 and K17 as pivotal targets for intervention.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Graphical abstract<\/jats:title>\n                    <jats:p>Our results indicate that FUT11-driven fucosylation is integral to the stabilization of K17 via K63 ubiquitination, thereby perpetuating psoriatic inflammation. Targeting FUT11 presents a novel therapeutic strategy for psoriasis management. This study highlights the critical interplay between glycosylation and ubiquitination in the pathophysiology of psoriasis, positioning FUT11 and K17 as pivotal targets for intervention.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s12964-025-02422-6","type":"journal-article","created":{"date-parts":[[2025,10,22]],"date-time":"2025-10-22T08:33:44Z","timestamp":1761122024000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["FUT11-Driven fucosylation coordinates K63 ubiquitination of keratin 17 to sustain psoriatic keratinocytes hyperproliferation"],"prefix":"10.1186","volume":"23","author":[{"given":"Xia","family":"Li","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guohao","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haijun","family":"Miao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lixin","family":"Yue","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jixin","family":"Gao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qingyang","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuai","family":"Shao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gang","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erle","family":"Dang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,10,22]]},"reference":[{"key":"2422_CR1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.893365","volume":"13","author":"B Radovani","year":"2022","unstructured":"Radovani B, Gudelj I. 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