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Volume 160, Issue 7

Sky1 regulates the expression of sulfur metabolism genes in response to cisplatin Free

Abstract

Cisplatin is commonly used in cancer therapy and yeast cells are also sensitive to this compound. We present a transcriptome analysis discriminating between RNA changes induced by cisplatin treatment, which are dependent on or independent of function – a gene whose deletion increases resistance to the drug. Gene expression changes produced by addition of cisplatin to W303 and W303-Δ cells were recorded using DNA microarrays. The data, validated by quantitative PCR, revealed 122 differentially expressed genes: 69 upregulated and 53 downregulated. Among the upregulated genes, those related to sulfur metabolism were over-represented and partially dependent on Sky1. Deletions of or other genes encoding co-regulators of the expression of sulfur-metabolism-related genes, with the exception of , did not modify the cisplatin sensitivity of yeast cells. One of the genes with the highest cisplatin-induced upregulation was , encoding a putative permease of sulfur compounds. We also measured the platinum, sulfur and glutathione content in W303, W303-Δ and W303-Δ cells after cisplatin treatment, and integration of the data suggested that these transcriptional changes might represent a cellular response that allowed chelation of cisplatin with sulfur-containing amino acids and also helped DNA repair by stimulating purine biosynthesis. The transcription pattern of stimulation of sulfur-containing amino acids and purine synthesis decreased, or even disappeared, in the W303-Δ strain.

  • Received:
  • Accepted:
  • Published Online:
Funding
This study was supported by the:
  • MICINN (Spain) co-financed by FEDER (CEE) (Award BFU2009-08854)
  • Xunta de Galicia (Award D.O.G. 10-10-2012. EN: 2012/118 and D.O.G. 3-12-2008 EN: 2008/008)
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2014-07-01
2024-04-19
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References

  1. Basu A., Krishnamurthy S. ( 2010). Cellular responses to cisplatin-induced DNA damage. J Nucleic Acids 2010:1–16 [View Article][PubMed]
     [Google Scholar]
  2. Benjamini Y., Hochberg Y. ( 1995). Controlling the false discovery rate: a practical and powerful approach to multiple testing. J R Stat Soc Series B Stat Methodol 57:289–300
     [Google Scholar]
  3. Berners-Price S. J., Kuchel P. W. ( 1990). Reaction of cis- and trans-[PtCl2(NH3)2] with reduced glutathione inside human red blood cells, studied by 1H and 15N-{1H} DEPT NMR. J Inorg Biochem 38:327–345 [View Article][PubMed]
     [Google Scholar]
  4. Birrell G. W., Brown J. A., Wu H. I., Giaever G., Chu A. M., Davis R. W., Brown J. M. ( 2002). Transcriptional response of Saccharomyces cerevisiae to DNA-damaging agents does not identify the genes that protect against these agents. Proc Natl Acad Sci U S A 99:8778–8783 [View Article][PubMed]
     [Google Scholar]
  5. Blaiseau P. L., Isnard A. D., Surdin-Kerjan Y., Thomas D. ( 1997). Met31p and Met32p, two related zinc finger proteins, are involved in transcriptional regulation of yeast sulfur amino acid metabolism. Mol Cell Biol 17:3640–3648[PubMed]
     [Google Scholar]
  6. Boubakari B. K., Bracht K., Neumann C., Grünert R., Bednarski P. J. ( 2004). No correlation between GSH levels in human cancer cell lines and the cell growth inhibitory activities of platinum diamine complexes. Arch Pharm (Weinheim) 337:668–671 [View Article][PubMed]
     [Google Scholar]
  7. Bracht K., Boubakari, Grünert R., Bednarski P. J. ( 2006). Correlations between the activities of 19 anti-tumor agents and the intracellular glutathione concentrations in a panel of 14 human cancer cell lines: comparisons with the National Cancer Institute data. Anticancer Drugs 17:41–51 [View Article][PubMed]
     [Google Scholar]
  8. Bradford M. M. ( 1976). A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem 72:248–254 [View Article][PubMed]
     [Google Scholar]
  9. Burger H., Capello A., Schenk P. W., Stoter G., Brouwer J., Nooter K. ( 2000). A genome-wide screening in Saccharomyces cerevisiae for genes that confer resistance to the anticancer agent cisplatin. Biochem Biophys Res Commun 269:767–774 [View Article][PubMed]
     [Google Scholar]
  10. Caba E., Dickinson D. A., Warnes G. R., Aubrecht J. ( 2005). Differentiating mechanisms of toxicity using global gene expression analysis in Saccharomyces cerevisiae. Mutat Res 575:34–46 [View Article][PubMed]
     [Google Scholar]
  11. Cavill R., Kamburov A., Ellis J. K., Athersuch T. J., Blagrove M. S., Herwig R., Ebbels T. M., Keun H. C. ( 2011). Consensus-phenotype integration of transcriptomic and metabolomic data implies a role for metabolism in the chemosensitivity of tumour cells. PLoS Comput Biol 7:e1001113 [View Article][PubMed]
     [Google Scholar]
  12. Dagher S. F., Fu X. D. ( 2001). Evidence for a role of Sky1p-mediated phosphorylation in 3′ splice site recognition involving both Prp8 and Prp17/Slu4. RNA 7:1284–1297 [View Article][PubMed]
     [Google Scholar]
  13. Denis V., Daignan-Fornier B. ( 1998). Synthesis of glutamine, glycine and 10-formyl tetrahydrofolate is coregulated with purine biosynthesis in Saccharomyces cerevisiae. Mol Gen Genet 259:246–255 [View Article][PubMed]
     [Google Scholar]
  14. Fauchon M., Lagniel G., Aude J. C., Lombardía L., Soularue P., Petat C., Marguerie G., Sentenac A., Werner M., Labarre J. ( 2002). Sulfur sparing in the yeast proteome in response to sulfur demand. Mol Cell 9:713–723 [View Article][PubMed]
     [Google Scholar]
  15. Fuertes M. A., Castilla J., Alonso C., Pérez J. M. ( 2003). Cisplatin biochemical mechanism of action: from cytotoxicity to induction of cell death through interconnections between apoptotic and necrotic pathways. Curr Med Chem 10:257–266 [View Article][PubMed]
     [Google Scholar]
  16. Gietz R. D., Akio S. ( 1988). New yeast–Escherichia coli shuttle vectors constructed with in vitro mutagenized yeast genes lacking six-base pair restriction sites. Gene 74:527–534 [View Article][PubMed]
     [Google Scholar]
  17. Gilbert W., Siebel C. W., Guthrie C. ( 2001). Phosphorylation by Sky1p promotes Npl3p shuttling and mRNA dissociation. RNA 7:302–313 [View Article][PubMed]
     [Google Scholar]
  18. Godwin A. K., Meister A., O’Dwyer P. J., Huang C. S., Hamilton T. C., Anderson M. E. ( 1992). High resistance to cisplatin in human ovarian cancer cell lines is associated with marked increase of glutathione synthesis. Proc Natl Acad Sci U S A 89:3070–3074 [View Article][PubMed]
     [Google Scholar]
  19. Hoffman C. S., Winston F. ( 1987). A ten-minute DNA preparation from yeast efficiently releases autonomous plasmids for transformation of Escherichia coli. Gene 57:267–272 [View Article][PubMed]
     [Google Scholar]
  20. Huang R. Y., Eddy M., Vujcic M., Kowalski D. ( 2005). Genome-wide screen identifies genes whose inactivation confer resistance to cisplatin in Saccharomyces cerevisiae. Cancer Res 65:5890–5897 [View Article][PubMed]
     [Google Scholar]
  21. Ishida S., Lee J., Thiele D. J., Herskowitz I. ( 2002). Uptake of the anticancer drug cisplatin mediated by the copper transporter Ctr1 in yeast and mammals. Proc Natl Acad Sci U S A 99:14298–14302 [View Article][PubMed]
     [Google Scholar]
  22. Isnard A. D., Thomas D., Surdin-Kerjan Y. ( 1996). The study of methionine uptake in Saccharomyces cerevisiae reveals a new family of amino acid permeases. J Mol Biol 262:473–484 [View Article][PubMed]
     [Google Scholar]
  23. Jin Y. H., Dunlap P. E., McBride S. J., Al-Refai H., Bushel P. R., Freedman J. H. ( 2008). Global transcriptome and deletome profiles of yeast exposed to transition metals. PLoS Genet 4:e1000053 [View Article][PubMed]
     [Google Scholar]
  24. Jordan P., Carmo-Fonseca M. ( 1998). Cisplatin inhibits synthesis of ribosomal RNA in vivo. Nucleic Acids Res 26:2831–2836 [View Article][PubMed]
     [Google Scholar]
  25. Kasherman Y., Sturup S., Gibson D. ( 2009). Is glutathione the major cellular target of cisplatin? A study of the interactions of cisplatin with cancer cell extracts. J Med Chem 52:4319–4328 [View Article][PubMed]
     [Google Scholar]
  26. Kim H. K., Choi I. J., Kim C. G., Kim H. S., Oshima A., Michalowski A., Green J. E. ( 2011). A gene expression signature of acquired chemoresistance to cisplatin and fluorouracil combination chemotherapy in gastric cancer patients. PLoS ONE 6:e16694 [View Article][PubMed]
     [Google Scholar]
  27. Komiya S., Gobhardt M. C., Mangham D. C., Inoue A. ( 1998). Role of glutathione in cisplatin resistance in osteosarcoma cell lines. J Orthop Res 16:15–22 [View Article][PubMed]
     [Google Scholar]
  28. Kuras L., Cherest H., Surdin-Kerjan Y., Thomas D. ( 1996). A heteromeric complex containing the centromere binding factor 1 and two basic leucine zipper factors, Met4 and Met28, mediates the transcription activation of yeast sulfur metabolism. EMBO J 15:2519–2529[PubMed]
     [Google Scholar]
  29. Lee T. A., Jorgensen P., Bognar A. L., Peyraud C., Thomas D., Tyers M. ( 2010). Dissection of combinatorial control by the Met4 transcriptional complex. Mol Biol Cell 21:456–469 [View Article][PubMed]
     [Google Scholar]
  30. Livak K. J., Schmittgen T. D. ( 2001). Analysis of relative gene expression data using real-time quantitative PCR and the 2–ΔΔCT method. Methods 25:402–408 [View Article][PubMed]
     [Google Scholar]
  31. Martins N. M., Santos N. A., Curti C., Bianchi M. L., Santos A. C. ( 2008). Cisplatin induces mitochondrial oxidative stress with resultant energetic metabolism impairment, membrane rigidification and apoptosis in rat liver. J Appl Toxicol 28:337–344 [View Article][PubMed]
     [Google Scholar]
  32. Medina I., Carbonell J., Pulido L., Madeira S. C., Goetz S., Conesa A., Tárraga J., Pascual-Montano A., Nogales-Cadenas R. & other authors ( 2010). Babelomics: an integrative platform for the analysis of transcriptomics, proteomics and genomic data with advanced functional profiling. Nucleic Acids Res 38:Web ServerW210–W213 [View Article][PubMed]
     [Google Scholar]
  33. Pérez R. P. ( 1998). Cellular and molecular determinants of cisplatin resistance. Eur J Cancer 34:1535–1542 [View Article][PubMed]
     [Google Scholar]
  34. Pratibha R., Sameer R., Rataboli P. V., Bhiwgade D. A., Dhume C. Y. ( 2006). Enzymatic studies of cisplatin induced oxidative stress in hepatic tissue of rats. Eur J Pharmacol 532:290–293 [View Article][PubMed]
     [Google Scholar]
  35. Rhieu S. Y., Urbas A. A., Lippa K. A., Reipa V. ( 2013). Quantitative measurements of glutathione in yeast cell lysate using 1H NMR. Anal Bioanal Chem 405:4963–4968 [View Article][PubMed]
     [Google Scholar]
  36. Robinson M. D., Grigull J., Mohammad N., Hughes T. R. ( 2002). FunSpec: a web-based cluster interpreter for yeast. BMC Bioinformatics 3:35 [View Article][PubMed]
     [Google Scholar]
  37. Rodríguez Lombardero S., Vizoso Vázquez A., Rodríguez Belmonte E., González Siso M. I., Cerdán M. E. ( 2012). SKY1 and IXR1 interactions, their effects on cisplatin and spermine resistance in Saccharomyces cerevisiae. Can J Microbiol 58:184–188 [View Article][PubMed]
     [Google Scholar]
  38. Schenk P. W., Boersma A. W., Brandsma J. A., den Dulk H., Burger H., Stoter G., Brouwer J., Nooter K. ( 2001). SKY1 is involved in cisplatin-induced cell kill in Saccharomyces cerevisiae, and inactivation of its human homologue, SRPK1, induces cisplatin resistance in a human ovarian carcinoma cell line. Cancer Res 61:6982–6986[PubMed]
     [Google Scholar]
  39. Schenk P. W., Boersma A. W., Brok M., Burger H., Stoter G., Nooter K. ( 2002). Inactivation of the Saccharomyces cerevisiae SKY1 gene induces a specific modification of the yeast anticancer drug sensitivity profile accompanied by a mutator phenotype. Mol Pharmacol 61:659–666 [View Article][PubMed]
     [Google Scholar]
  40. Shen H., Green M. R. ( 2006). RS domains contact splicing signals and promote splicing by a common mechanism in yeast through humans. Genes Dev 20:1755–1765 [View Article][PubMed]
     [Google Scholar]
  41. Smyth G. K. ( 2005). LIMMA: linear models for microarray data. Bioinformatics and Computational Biology Solutions using R and Bioconductor397–420 Gentleman R., Carey V., Dudoit S., Irizarry R., Huber W. New York: Springer; [View Article]
     [Google Scholar]
  42. Tizón B., Rodríguez-Torres A. M., Cerdán M. E. ( 1999). Disruption of six novel Saccharomyces cerevisiae genes reveals that YGL129c is necessary for growth in non-fermentable carbon sources, YGL128c for growth at low or high temperatures and YGL125w is implicated in the biosynthesis of methionine. Yeast 15:145–154 [View Article][PubMed]
     [Google Scholar]
  43. Wan Y. W., Sabbagh E., Raese R., Qian Y., Luo D., Denvir J., Vallyathan V., Castranova V., Guo N. L. ( 2010). Hybrid models identified a 12-gene signature for lung cancer prognosis and chemoresponse prediction. PLoS ONE 5:e12222 [View Article][PubMed]
     [Google Scholar]
  44. Windgassen M., Krebber H. ( 2003). Identification of Gbp2 as a novel poly(A)+ RNA-binding protein involved in the cytoplasmic delivery of messenger RNAs in yeast. EMBO Rep 4:278–283 [View Article][PubMed]
     [Google Scholar]
  45. Windgassen M., Sturm D., Cajigas I. J., González C. I., Seedorf M., Bastians H., Krebber H. ( 2004). Yeast shuttling SR proteins Npl3p, Gbp2p, and Hrb1p are part of the translating mRNPs, and Npl3p can function as a translational repressor. Mol Cell Biol 24:10479–10491 [View Article][PubMed]
     [Google Scholar]
  46. Wu H. I., Brown J. A., Dorie M. J., Lazzeroni L., Brown J. M. ( 2004). Genome-wide identification of genes conferring resistance to the anticancer agents cisplatin, oxaliplatin, and mitomycin C. Cancer Res 64:3940–3948 [View Article][PubMed]
     [Google Scholar]
  47. Zimmermann T., Zeizinger M., Burda J. V. ( 2005). Cisplatin interaction with cysteine and methionine, a theoretical DFT study. J Inorg Biochem 99:2184–2196 [View Article][PubMed]
     [Google Scholar]
  48. Zitomer R. S., Hall B. D. ( 1976). Yeast cytochrome c messenger RNA. In vitro translation and specific immunoprecipitation of the CYC1 gene product. J Biol Chem 251:6320–6326[PubMed]
     [Google Scholar]
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Sky1 regulates the expression of sulfur metabolism genes in response to cisplatin
Microbiology 160, 1357 (2014); https://doi.org/10.1099/mic.0.078402-0
/content/journal/micro/10.1099/mic.0.078402-0
/content/journal/micro/10.1099/mic.0.078402-0
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