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Korean Society for Biochemistry and Molecular Biology (생화학분자생물학회)
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Phosphorylation of rpS3 by Lyn increases translation of Multi-Drug Resistance (MDR1) gene

  • Woo Sung Ahn (Laboratory of Biochemistry, Division of Life Sciences, Korea University) ;
  • Hag Dong Kim (HAEL Lab, TechnoComplex, Korea University) ;
  • Tae Sung Kim (Laboratory of Biochemistry, Division of Life Sciences, Korea University) ;
  • Myoung Jin Kwak (Laboratory of Biochemistry, Division of Life Sciences, Korea University) ;
  • Yong Jun Park (Laboratory of Biochemistry, Division of Life Sciences, Korea University) ;
  • Joon Kim (Laboratory of Biochemistry, Division of Life Sciences, Korea University)
  • Received : 2022.09.20
  • Accepted : 2023.02.01
  • Published : 2023.05.31
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Abstract

Lyn, a tyrosine kinase that is activated by double-stranded DNA-damaging agents, is involved in various signaling pathways, such as proliferation, apoptosis, and DNA repair. Ribosomal protein S3 (RpS3) is involved in protein biosynthesis as a component of the ribosome complex and possesses endonuclease activity to repair damaged DNA. Herein, we demonstrated that rpS3 and Lyn interact with each other, and the phosphorylation of rpS3 by Lyn, causing ribosome heterogeneity, upregulates the translation of p-glycoprotein, which is a gene product of multidrug resistance gene 1. In addition, we found that two different regions of the rpS3 protein are associated with the SH1 and SH3 domains of Lyn. An in vitro immunocomplex kinase assay indicated that the rpS3 protein acts as a substrate for Lyn, which phosphorylates the Y167 residue of rpS3. Furthermore, by adding various kinase inhibitors, we confirmed that the phosphorylation status of rpS3 was regulated by both Lyn and doxorubicin, and the phosphorylation of rpS3 by Lyn increased drug resistance in cells by upregulating p-glycoprotein translation.

Keywords

Acknowledgement

This study was supported in part by Korea University Grant, NRF-2020R1A2C2100803, 2019S1A5A2A03050121 and NRF-2021R1A6A1A10045235.

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