Phosphorylation of rpS3 by Lyn increases translation of Multi-Drug Resistance (MDR1) gene
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Lyn, a tyrosine kinase that is activated by double-stranded DNAdamagingagents, is involved in various signaling pathways,such as proliferation, apoptosis, and DNA repair. Ribosomalprotein S3 (RpS3) is involved in protein biosynthesis as a componentof the ribosome complex and possesses endonucleaseactivity to repair damaged DNA. Herein, we demonstrated thatrpS3 and Lyn interact with each other, and the phosphorylationof rpS3 by Lyn, causing ribosome heterogeneity, upregulatesthe translation of p-glycoprotein, which is a gene product of multidrugresistance gene 1. In addition, we found that two differentregions of the rpS3 protein are associated with the SH1 and SH3domains of Lyn. An in vitro immunocomplex kinase assay indicatedthat the rpS3 protein acts as a substrate for Lyn, whichphosphorylates the Y167 residue of rpS3. Furthermore, by addingvarious kinase inhibitors, we confirmed that the phosphorylationstatus of rpS3 was regulated by both Lyn and doxorubicin,and the phosphorylation of rpS3 by Lyn increased drug resistancein cells by upregulating p-glycoprotein translation.
Abstract
Lyn, a tyrosine kinase that is activated by double-stranded DNAdamagingagents, is involved in various signaling pathways,such as proliferation, apoptosis, and DNA repair. Ribosomalprotein S3 (RpS3) is involved in protein biosynthesis as a componentof the ribosome complex and possesses endonucleaseactivity to repair damaged DNA. Herein, we demonstrated thatrpS3 and Lyn interact with each other, and the phosphorylationof rpS3 by Lyn, causing ribosome heterogeneity, upregulatesthe translation of p-glycoprotein, which is a gene product of multidrugresistance gene 1. In addition, we found that two differentregions of the rpS3 protein are associated with the SH1 and SH3domains of Lyn. An in vitro immunocomplex kinase assay indicatedthat the rpS3 protein acts as a substrate for Lyn, whichphosphorylates the Y167 residue of rpS3. Furthermore, by addingvarious kinase inhibitors, we confirmed that the phosphorylationstatus of rpS3 was regulated by both Lyn and doxorubicin,and the phosphorylation of rpS3 by Lyn increased drug resistancein cells by upregulating p-glycoprotein translation.
참고문헌 (38)
- Kim J, "Implication of mammalian ribosomal protein S3in the processing of DNA damage", J Biol Chem, 270, pp.13620~13629 (1995)
- Yacoub A, "A Drosophila ribosomal protein contains 8-oxoguanine and abasic site DNA repair activities", EMBO J, 15, pp.2306~2312 (1996)
- Jung SO, "Yeast ribosomal protein S3has an endonuclease activity on AP DNA", Mol Cells, 12, pp.84~90 (2001)
- Chang Hoon Lee, "Electron Paramagnetic Resonance Study Reveals a Putative Iron-Sulfur Cluster in Human rpS3 Protein", Molecules and Cells, 13(1), pp.154~156 (2002), 한국분자세포생물학회
- Kanno S, "Repair of apurinic", apyrimidinic sites by UV damage endonuclease;a repair protein for UV and oxidative damage, 1999, pp.27, 3096~3103
- Hegde V, "Conversion of the bifunctional 8-oxoguanine", beta-delta apurinic, J Biol Chem, pp.2001, 276[DOI]
- Kim Y, "Ribosomal protein S3 is secreted as a homodimer in cancer cells", Biochem Biophys Res Commun, 441, pp.805~808 (2013)
- Kim Y, "Ribosomal protein S3(rpS3)secreted from various cancer cells is N-linked glycosylated", Oncotarget, 7, pp.80350~80362 (2016)
- Hua W, "Over-expression of rps3 promotes acute lymphoblastic leukemia growth and progress by down-regulating COX-2 through NF-κb pathway", Blood, 128, pp.3927~ (2016)
- Kim SH, "Characterization of a wide range base-damage-endonuclease activity of mammalian rpS3", Biochem Biophys Res Commun, 328, pp.962~967 (2005)
- Kim TS, "PKCdelta-dependent functional switch of rpS3 between translation and DNA repair", Biochim Biophys Acta, 1793, pp.395~405 (2009)
- Jang CY, "RpS3, a DNA repair endonuclease and ribosomal protein, is involved in apoptosis", FEBS Lett, 560, pp.81~85 (2004)
- Park YJ, "Ribosomal protein S3 associates with the TFIIH complex and positively regulates nucleotide excision repair", Cell Mol Life Sci, 78, pp.3591~3606 (2021)
- Jang CY, "Ribosomal protein S3 is stabilized by sumoylation", Biochem Biophys Res Commun, 414, pp.523~527 (2011)
- Yi TL, "Hematopoietic cells express two forms of lyn kinase differing by 21 amino acids in the amino terminus", Mol Cell Biol, 11, pp.2391~2398 (1991)
- Yamanashi Y, "Association of B cell antigen receptor with protein tyrosine kinase Lyn", Science, 251, pp.192~194 (1991)
- Suzuki T, "Essential roles of Lyn in fibronectin-mediated filamentous actin assembly and cell motility in mast cells", J Immunol, 161, pp.3694~3701 (1998)
- Grishin A, "Involvement of Shc and Cbl-PI 3-kinase in Lyn-dependent proliferative signaling pathways for G-CSF", Oncogene, 19, pp.97~105 (2000)
- Corey SJ, "Requirement of Src kinase Lyn for induction of DNA synthesis by granulocyte colony-stimulating factor", J Biol Chem, 273, pp.3230~3235 (1998)
- Mayer BJ, "SH3 domains : complexity in moderation", J Cell Sci, 114, pp.1253~1263 (2001)
- Kharbanda S, "Nuclear signaling induced by ionizing radiation involves colocalization of the activated p56", p53lyn tyrosine kinase with p34cdc2, 1996, pp.56, 3617~3621
- DeFranco AL, "Positive and negative roles of the tyrosine kinase Lyn in B cell function", Semin Immunol, 10, pp.299~307 (1998)
- Yoshida K, "Role for Lyn tyrosine kinase as a regulator of stress-activated protein kinase activity in response to DNA damage", Mol Cell Biol, 20, pp.5370~5380 (2000)
- Hu Y, "Requirement of Src kinases Lyn, Hck and Fgr for BCR-ABL1-induced B-lymphoblastic leukemia but not chronic myeloid leukemia", Nat Genet, 36, pp.453~461 (2004)
- Satake K, "Human ABCB1confers cells resistance to cytotoxic guanidine alkaloids from Pterogyne nitens", Biomed Mater Eng, 25, pp.249~256 (2015)
- Fojo AT, "Expression of a multidrugresistance gene in human tumors and tissues", Proc Natl Acad Sci U S A, 84, pp.265~269 (1987)
- Baudis M, "ABCB1 over-expression and drug-efflux in acute lymphoblastic leukemia cell lines with t(17;19)and E2A-HLF expression", Pediatr Blood Cancer, 47, pp.757~764 (2006)
- Arceci RJ, "Multidrug resistance gene expression is controlled by steroid hormones in the secretory epithelium of the uterus", Mol Reprod Dev, 25, pp.101~109 (1990)
- Lelong-Rebel IH, "Differential phosphorylation patterns of P-glycoprotein reconstituted into a proteoliposome system: insight into additional unconventional phosphorylation sites", Anticancer Res, 25, pp.3925~3935 (2005)
- Kuo MT, "Redox regulation of multidrug resistance in cancer chemotherapy : molecular mechanisms and therapeutic opportunities", Antioxid Redox Signal, 11, pp.99~133 (2009)
- Meredith AM, "Increasing role of the cancer chemotherapeutic doxorubicin in cellular metabolism", J Pharm Pharmacol, 68, pp.729~741 (2016)
- Thomas H, "Overcoming multidrug resistance in cancer : an update on the clinical strategy of inhibiting p-glycoprotein", Cancer Control, 10, pp.159~165 (2003)
- Kim TS, "Interaction of Hsp90 with ribosomal proteins protects from ubiquitination and proteasome-dependent degradation", Mol Biol Cell, 17, pp.824~833 (2006)
- 김태성, "JNK activation induced by ribotoxic stress is initiated from 80S monosomes but not polysomes", BMB Reports, 52(8), pp.502~507 (2019), 생화학분자생물학회[DOI]
- Beausoleil SA, "A probability-based approach for high-throughput protein phosphorylation analysis and site localization", Nat Biotechnol, 24, pp.1285~1292 (2006)
- Shin HS, "Arginine methylation of ribosomal protein S3 affects ribosome assembly", Biochem Biophys Res Commun, 385, pp.273~278 (2009)
- 정유진, "Modulating cellular balance of Rps3 mono-ubiquitination by both Hel2 E3 ligase and Ubp3 deubiquitinase regulates protein quality control", Experimental and Molecular Medicine, 49, pp.1~12 (2017), 생화학분자생물학회
- Yang HW, "Senescent cells differentially translate senescence-related mRNAs via ribosome heterogeneity", J Gerontol A Biol Sci Med Sci, 74, pp.1015~1024 (2019)