biostudies-literatureUnknown15(10)Ryu SRibosomal 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-Cullin1-F-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-Biomolecules1350https://www.ebi.ac.uk/biostudies/studies/S-EPMC12561996biostudies-literatureCritical Role of RPS4X in Modulating SCF Complex Formation and Cell Survival.PMC12561996Tanaka YBando SOhshima TMukai RIshihara YTominaga TKim MJRyu SfalseCritical Role of RPS4X in Modulating SCF Complex Formation and Cell Survival.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-Cullin1-F-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-2025-01-01T00:00:00Z2025 Sep2026-05-15T03:14:28.886Z2026-05-15T03:08:40.916ZS-EPMC125619964115457910.3390/biom15101350