SKY1 and IXR1 interactions, their effects on cisplatin and spermine resistance in Saccharomyces cerevisiae

Lombardero, Silvia Rodríguez; Vizoso-Vázquez, Ángel; Rodrı́guez-Belmonte, Esther; González-Siso, María-Isabel; Cerdán, M. Esperanza

doi:10.1139/w11-124

Cited by 5 publications

(9 citation statements)

References 18 publications

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“…S . cerevisiae strain W303 (MATa ade 2-1 can 1-100 leu 2-3,112 trp 1-100 ura 3-52) and its derivative, W303- ixr1Δ (previously described by 94 , have been used in the transcriptome experiments. S .…”

Section: Methodsmentioning

confidence: 99%

Ixr1 Regulates Ribosomal Gene Transcription and Yeast Response to Cisplatin

Vizoso-Vázquez

Lamas-Maceiras

González-Siso

et al. 2018

Sci Rep

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Ixr1 is a Saccharomyces cerevisiae HMGB protein that regulates the hypoxic regulon and also controls the expression of other genes involved in the oxidative stress response or re-adaptation of catabolic and anabolic fluxes when oxygen is limiting. Ixr1 also binds with high affinity to cisplatin-DNA adducts and modulates DNA repair. The influence of Ixr1 on transcription in the absence or presence of cisplatin has been analyzed in this work. Ixr1 regulates other transcriptional factors that respond to nutrient availability or extracellular and intracellular stress stimuli, some controlled by the TOR pathway and PKA signaling. Ixr1 controls transcription of ribosomal RNAs and genes encoding ribosomal proteins or involved in ribosome assembly. qPCR, ChIP, and 18S and 25S rRNAs measurement have confirmed this function. Ixr1 binds directly to several promoters of genes related to rRNA transcription and ribosome biogenesis. Cisplatin treatment mimics the effect of IXR1 deletion on rRNA and ribosomal gene transcription, and prevents Ixr1 binding to specific promoters related to these processes.

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Section: Methodsmentioning

confidence: 99%

Ixr1 Regulates Ribosomal Gene Transcription and Yeast Response to Cisplatin

Vizoso-Vázquez

Lamas-Maceiras

González-Siso

et al. 2018

Sci Rep

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“…Here, we obtained a set of 122 differentially expressed genes: 69 upregulated (Table S1) and 53 downregulated (Table S2). The observed differences might be explained because the effect of cisplatin treatment is strain-dependent (Rodríguez Lombardero et al , 2012), and also varies in relation to cell culture and treatment conditions, these being different in the two studies.…”

Section: Resultsmentioning

confidence: 94%

“…The S. cerevisiae strain W303 ( MATa ade2-1 can1-100 his3-11,15 leu2-3,112 trp1-100 ura3-52 ) and its derivative W303-Δ sky1 have been described previously (Rodríguez Lombardero et al , 2012) and were used in these analyses. The S. cerevisiae strains yMT-1465 ( ade2-1 can1-100 his3-1,15 leu2-3,112 trp1-1 ura3 met31 : : TRP1 met32 : : HIS3 ), yMT1782 ( ade2-1 can1-100 his3-1,15 leu2-3,112 trp1-1 ura3 met28 : : LEU2 ), yMT1813 ( ade2-1 can1-100 his3-1,15 leu2-3,112 trp1-1 ura3-52met4 : : TRP1 ) and yMT1947 ( ade2-1 can1-100 his3-1,15 leu2-3,112 trp1-1 ura3 cbf1 : : TRP1 ) were also W303 derivatives and have been described previously (Lee et al , 2010).…”

Section: Methodsmentioning

confidence: 99%

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

et al. 2014

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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 SKY1 function – a gene whose deletion increases resistance to the drug. Gene expression changes produced by addition of cisplatin to W303 and W303-Δsky1 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 MET4 or other genes encoding co-regulators of the expression of sulfur-metabolism-related genes, with the exception of MET28, did not modify the cisplatin sensitivity of yeast cells. One of the genes with the highest cisplatin-induced upregulation was SEO1, encoding a putative permease of sulfur compounds. We also measured the platinum, sulfur and glutathione content in W303, W303-Δsky1 and W303-Δseo1 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-Δsky1 strain.

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“…The construction of the Δsky1 strain has been previously described [49]. The strains Δmmi1 , Δbmh1 , Δbmh2 , and their isogenic parental strain BY4741 were obtained from EUROSCARF [50].…”

Section: Methodsmentioning

confidence: 99%

Proteomic Analyses Reveal that Sky1 Modulates Apoptosis and Mitophagy in Saccharomyces cerevisiae Cells Exposed to Cisplatin

Rodríguez-Lombardero

Rodrı́guez-Belmonte

González-Siso

et al. 2014

IJMS

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Sky1 is the only member of the SR (Serine–Arginine) protein kinase family in Saccharomyces cerevisiae. When yeast cells are treated with the anti-cancer drug cisplatin, Sky1 kinase activity is necessary to produce the cytotoxic effect. In this study, proteome changes in response to this drug and/or SKY1 deletion have been evaluated in order to understand the role of Sky1 in the response of yeast cells to cisplatin. Results reveal differential expression of proteins previously related to the oxidative stress response, DNA damage, apoptosis and mitophagy. With these precedents, the role of Sky1 in apoptosis, necrosis and mitophagy has been evaluated by flow-cytometry, fluorescence microscopy, biosensors and fluorescence techniques. After cisplatin treatment, an apoptotic-like process diminishes in the ∆sky1 strain in comparison to the wild-type. The treatment does not affect mitophagy in the wild-type strain, while an increase is observed in the ∆sky1 strain. The increased resistance to cisplatin observed in the ∆sky1 strain may be attributable to a decrease of apoptosis and an increase of mitophagy.

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SKY1 and IXR1 interactions, their effects on cisplatin and spermine resistance in Saccharomyces cerevisiae

Cited by 5 publications

References 18 publications

Ixr1 Regulates Ribosomal Gene Transcription and Yeast Response to Cisplatin

Ixr1 Regulates Ribosomal Gene Transcription and Yeast Response to Cisplatin

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

Proteomic Analyses Reveal that Sky1 Modulates Apoptosis and Mitophagy in Saccharomyces cerevisiae Cells Exposed to Cisplatin

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