Publicação
Identification of genes and the signal transduction pathways involved in the regulation of acetic acid-induced programmed cell death
| Resumo: | After many years of research, S. cerevisiae was accepted as a powerful model that allows increasing our comprehension about the underlying mechanisms of apoptosis in more complex and less accessible organisms. So, to better understand these apoptotic mechanisms we performed a functional analysis, at whole-genome scale, with the Euroscarf mutants collection. This analysis reveled 2159 resistant mutants and 391 mutants more sensitive to acetic acid induced cell death than the parental strain BY4741. The results obtained contribute to further characterize acetic acid-induced programmed cell death (PCD), and provide information on new putative targets for its control. Most of the studies on apoptosis in yeast have been centered in the identification of apoptotic markers, however less is known about the signal transduction pathways that induce apoptosis. Cells possess a network of signal transduction pathways, which allow them to respond to different stimulus, implying several changes in genetic expression. Sfl1p is a transcription factor (TF) involved in repression of flocculation-related genes, and activation of stress responsive genes. We studied, cell death induced by acetic acid in yeast strains deleted in SFL1 and in genes potentially regulated by Sfl1p (AQY2, FMP42, FMP45, SUC2, HSP30, HSP104, NNF2, FLO1 FLO8, YMR173W-a, YJR11W e YCR006C). The results obtained suggest that Sfl1p and the genes under its regulation, share a role in the mediation of acetic acid-induced apoptosis. Slf1p harbors 3 domains characteristic of the c-myc oncoprotein, a transcription factor with an important role in apoptosis induction and often found mutated in cancer cells. Our results showing that Sfl1p is also involved in the regulation of apoptosis in yeast suggest that these domains can have a conserved function in apoptosis regulation across kingdoms. We also studied the involvement of genes regulated by Rlm1p on cell death induced by acetic acid. This TF coordinates an adaptive transcriptional response to the stress induced in the cell wall. Our results show that the genes that confer stability to the cell wall, confers sensitivity to acetic acid, when mutated. On the other hand, the genes involved in the cell wall formation, confers resistance, when mutated. |
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| Autores principais: | Duarte, Ana Marta Gomes |
| Ano: | 2013 |
| País: | Portugal |
| Tipo de documento: | dissertação de mestrado |
| Tipo de acesso: | acesso aberto |
| Instituição associada: | Universidade do Minho |
| Idioma: | inglês |
| Origem: | RepositóriUM - Universidade do Minho |
| Resumo: | After many years of research, S. cerevisiae was accepted as a powerful model that allows increasing our comprehension about the underlying mechanisms of apoptosis in more complex and less accessible organisms. So, to better understand these apoptotic mechanisms we performed a functional analysis, at whole-genome scale, with the Euroscarf mutants collection. This analysis reveled 2159 resistant mutants and 391 mutants more sensitive to acetic acid induced cell death than the parental strain BY4741. The results obtained contribute to further characterize acetic acid-induced programmed cell death (PCD), and provide information on new putative targets for its control. Most of the studies on apoptosis in yeast have been centered in the identification of apoptotic markers, however less is known about the signal transduction pathways that induce apoptosis. Cells possess a network of signal transduction pathways, which allow them to respond to different stimulus, implying several changes in genetic expression. Sfl1p is a transcription factor (TF) involved in repression of flocculation-related genes, and activation of stress responsive genes. We studied, cell death induced by acetic acid in yeast strains deleted in SFL1 and in genes potentially regulated by Sfl1p (AQY2, FMP42, FMP45, SUC2, HSP30, HSP104, NNF2, FLO1 FLO8, YMR173W-a, YJR11W e YCR006C). The results obtained suggest that Sfl1p and the genes under its regulation, share a role in the mediation of acetic acid-induced apoptosis. Slf1p harbors 3 domains characteristic of the c-myc oncoprotein, a transcription factor with an important role in apoptosis induction and often found mutated in cancer cells. Our results showing that Sfl1p is also involved in the regulation of apoptosis in yeast suggest that these domains can have a conserved function in apoptosis regulation across kingdoms. We also studied the involvement of genes regulated by Rlm1p on cell death induced by acetic acid. This TF coordinates an adaptive transcriptional response to the stress induced in the cell wall. Our results show that the genes that confer stability to the cell wall, confers sensitivity to acetic acid, when mutated. On the other hand, the genes involved in the cell wall formation, confers resistance, when mutated. |
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