{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T21:42:27Z","timestamp":1792618947449,"version":"4.5.0"},"reference-count":46,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2025,9,23]],"date-time":"2025-09-23T00:00:00Z","timestamp":1758585600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"JSPS KAKENHI","award":["JP15H06790"],"award-info":[{"award-number":["JP15H06790"]}]},{"name":"JSPS KAKENHI","award":["JP26430128"],"award-info":[{"award-number":["JP26430128"]}]},{"name":"Japanese Leukemia Research Foundation","award":["JP15H06790"],"award-info":[{"award-number":["JP15H06790"]}]},{"name":"Japanese Leukemia Research Foundation","award":["JP26430128"],"award-info":[{"award-number":["JP26430128"]}]},{"name":"L\u2019Or\u00e9al-UNESCO for Woman in Science Fellowship Program","award":["JP15H06790"],"award-info":[{"award-number":["JP15H06790"]}]},{"name":"L\u2019Or\u00e9al-UNESCO for Woman in Science Fellowship Program","award":["JP26430128"],"award-info":[{"award-number":["JP26430128"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Ribosomal proteins have long been recognized as vital components of ribosomes that are involved in protein synthesis. However, emerging evidence indicates that some ribosomal proteins exhibit extraribosomal functions. In this study, we investigated the role of the ribosomal protein S4 X-linked (RPS4X) in the regulation of the Skp1\u2013Cullin1\u2013F-box (SCF) ubiquitin ligase complex and apoptosis. We found that RPS4X expression interfered with SCF complex formation by disrupting the interaction between Cullin1 and Skp1. This disruption suppressed ubiquitination of multiple SCF complex substrates, including the anti-apoptotic proteins myeloid cell leukemia 1 (MCL1) and HS1-associated protein X1 (HAX1). Stabilization of MCL1 and HAX1 by RPS4X led to increased resistance of HeLa cells to doxorubicin-induced apoptosis. These findings suggest that RPS4X contributes to the regulation of protein homeostasis and apoptotic pathways by modulating SCF complex activity, providing new insights into the extraribosomal roles of ribosomal proteins.<\/jats:p>","DOI":"10.3390\/biom15101350","type":"journal-article","created":{"date-parts":[[2025,9,23]],"date-time":"2025-09-23T10:27:53Z","timestamp":1758623273000},"page":"1350","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Critical Role of RPS4X in Modulating SCF Complex Formation and Cell Survival"],"prefix":"10.3390","volume":"15","author":[{"given":"Satsuki","family":"Ryu","sequence":"first","affiliation":[{"name":"Faculty of Pharmaceutical Science at Kagawa Campus, Tokushima Bunri University, Takamatsu 760-8542, Kagawa, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min Ji","family":"Kim","sequence":"additional","affiliation":[{"name":"Faculty of Pharmaceutical Science at Kagawa Campus, Tokushima Bunri University, Takamatsu 760-8542, Kagawa, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuya","family":"Bando","sequence":"additional","affiliation":[{"name":"Faculty of Science and Engineering, Tokushima Bunri University, Takamatsu 760-8542, Kagawa, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuka","family":"Tanaka","sequence":"additional","affiliation":[{"name":"Faculty of Science and Engineering, Tokushima Bunri University, Takamatsu 760-8542, Kagawa, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4669-4100","authenticated-orcid":false,"given":"Risa","family":"Mukai","sequence":"additional","affiliation":[{"name":"Department of Cell Biology and Molecular Medicine, Rutgers New Jersey Medical School, Newark, NJ 07103, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasuhiro","family":"Ishihara","sequence":"additional","affiliation":[{"name":"Program of Biomedical Science, Graduate School of Integrated Sciences for Life, Hiroshima University, Hiroshima 739-8521, Hiroshima, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1078-7989","authenticated-orcid":false,"given":"Takashi","family":"Tominaga","sequence":"additional","affiliation":[{"name":"Faculty of Pharmaceutical Science at Kagawa Campus, Tokushima Bunri University, Takamatsu 760-8542, Kagawa, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takayuki","family":"Ohshima","sequence":"additional","affiliation":[{"name":"Faculty of Science and Engineering, Tokushima Bunri University, Takamatsu 760-8542, Kagawa, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,9,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1038\/nrm1547","article-title":"Function and regulation of cullin\u2013RING ubiquitin ligases","volume":"6","author":"Petroski","year":"2005","journal-title":"Nat. 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