Phosphorylation of rpS3 by Lyn increases translation of Multi-Drug Resistance (MDR1) gene

Woo Sung Ahn, Hag Dong Kim, Tae Sung Kim, Myoung Jin Kwak, Yong Jun Park, Joon Kim

Research output: Contribution to journalArticlepeer-review

1 Citation (Scopus)

Abstract

Lyn, a tyrosine kinase that is activated by double-stranded DNAdamaging 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.

Original languageEnglish
Pages (from-to)302-307
Number of pages6
JournalBMB reports
Volume56
Issue number5
DOIs
Publication statusPublished - 2023

Bibliographical note

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

Publisher Copyright:
© 2023 by the The Korean Society for Biochemistry and Molecular Biology

Keywords

  • Drug resistance
  • Lyn
  • MDR1
  • Ribosome heterogeneity
  • RpS3

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology

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