Phosphorylation of YBX1 in the kidneys is altered in legumain knockout-mice

Sever, Tilen (author), Sinožić, Tea (author), Kolarič, Matej (author), Turk, Boris (author), Fonović, Marko (author)

Protein phosphorylation is a common post-translational modification that plays a crucial role in cellular signal transduction. Disruptions in this process can lead to phenotypic deviations in healthy organisms. Legumain is a cysteine proteinase present in plants and animals. Legumain is involved in the regulation of kidney and hematopoietic homeostasis, as well as immune response. Its dysregulation is associated with various types of cancers and neurodegenerative diseases. Legumain knockout mice generally exhibit a normal phenotype, except for altered kidney function, hemophagocytic syndrome, and extramedullary hematopoiesis. In this study, we analyzed the changes in protein phosphorylation in legumain knockout mice compared to their wild-type counterparts to elucidate how legumain deficiency affects protein phosphorylation and related cell signaling. Phosphopeptides from the kidney and liver samples were enriched and analyzed using mass spectrometry and validated with Western blot and immunohistochemistry. Several phosphorylation sites on the RNA- and DNA-binding protein Y-box binding protein 1 were identified. A site on the serine 100 residue was found to activate the NF-κB pathway in legumain knockout mice, resulting in an enhanced inflammatory response. This was supported by the increased expression of several NF-κB genes. Overall, this study provides valuable insights into the role of legumain and its impact on various cellular processes.

• Language: English
• Keywords: legumain, knockout mice, cellular signal transduction, YBX1, phosphorylation
• Work type: Article
• Typology: 1.01 - Original Scientific Article
• Organization: MF - Faculty of Medicine; FKKT - Faculty of Chemistry and Chemical Technology
• Publication status: Published
• Publication version: Version of Record
• Year: 2026
• Number of pages: Str. 3078-3091
• Numbering: Vol. 25, iss. 6
• PID: 20.500.12556/RUL-189587
• UDC: 577
• ISSN on article: 1535-3907
• DOI: 10.1021/acs.jproteome.6c00105
• COBISS.SI-ID: 281767683
• Publication date in RUL: 09.10.2026

Record is a part of a journal

• Title: Journal of proteome research
• Shortened title: J. proteome res.
• Publisher: American Chemical Society
• ISSN: 1535-3907
• COBISS.SI-ID: 513576473

Licences

• License: CC BY 4.0, Creative Commons Attribution 4.0 International
• Link: http://creativecommons.org/licenses/by/4.0/
• Description: This is the standard Creative Commons license that gives others maximum freedom to do what they want with the work as long as they credit the author.

Secondary language

• Language: Slovenian
• Keywords: legumain, ledvice, fosforilacija

Projects

• Funder: ARIS - Slovenian Research and Innovation Agency
• Project number: J1-3022
• Name: Sistemska določitev fizioloških vlog legumaina

• Funder: ARIS - Slovenian Research and Innovation Agency
• Project number: P1-0140
• Name: Proteoliza in njena regulacija pri zdravju in boleznih