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Quantitative proteomic analysis reveals posttranslational responses to aneuploidy in yeast.

Dephoure N, Hwang S, O'Sullivan C, Dodgson SE, Gygi SP, Amon A, Torres EM - Elife (2014)

Bottom Line: Our proteomic analyses further revealed a novel aneuploidy-associated protein expression signature characteristic of altered metabolism and redox homeostasis.Interestingly, increased protein turnover attenuates ROS levels and this novel aneuploidy-associated signature and improves the fitness of most aneuploid strains.Our results show that aneuploidy causes alterations in metabolism and redox homeostasis.

View Article: PubMed Central - PubMed

Affiliation: Department of Cell Biology, Harvard Medical School, Boston, United States.

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Related in: MedlinePlus

APS in the meiotically generated aneuploid strains.(A) Comparison of protein levels of the APS in five aneuploidy strains from Pavelka et al. (2010). Averaged protein (red bars) expression of the APS of each aneuploid strain are shown below. Error bars represent SEM. (B) Correlation of the average APS and chromosome size in five aneuploidy strains from Pavelka et al. (2010). Linear fit is shown in dashed line.DOI:http://dx.doi.org/10.7554/eLife.03023.026
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fig6s2: APS in the meiotically generated aneuploid strains.(A) Comparison of protein levels of the APS in five aneuploidy strains from Pavelka et al. (2010). Averaged protein (red bars) expression of the APS of each aneuploid strain are shown below. Error bars represent SEM. (B) Correlation of the average APS and chromosome size in five aneuploidy strains from Pavelka et al. (2010). Linear fit is shown in dashed line.DOI:http://dx.doi.org/10.7554/eLife.03023.026

Mentions: GO enrichment analysis of the APS revealed a group of proteins associated with cellular responses to oxidative stress, including thioredoxins Trx1 and Trx2, oxidoreductases Grx1 and Grx5, peroxiredoxins Ahp1 and Prx1, and the superoxide dismutase Sod1. In addition, the APS included proteins upregulated during oxidative stress such as the yeast orthologue of the translationally controlled tumor protein (p23) Tma19, the essential NTPase required for ribosome synthesis Fap7, the 3′-5′-exodeoxyribonuclease YBL055C, and the polyamine synthases Spe3 and Spe4 (Gasch et al., 2000; Juhnke et al., 2000; Chattopadhyay et al., 2006). These results indicate that aneuploid cells may be exposed to higher levels of intracellular reactive oxygen species (ROS) (see below). Another GO category of APS-enriched genes is ‘metabolic processes’, including functions such as amino acid biosynthesis and cellular bioenergetics. Interestingly, the intensity of the APS, measured as the average increase of its 92 proteins, correlated with the size of the additional chromosome (Pearson r = 0.62, Figure 6B), indicating that it may be a direct consequence of the cellular imbalances caused by the presence of the extra chromosome, rather than due to increased dosage of specific genes. In addition, we found that the APS is also present in aneuploid strains isolated from random meiosis and that its intensity also correlated with the size of the additional chromosomes in those aneuploid strains (Figure 6—figure supplement 2).


Quantitative proteomic analysis reveals posttranslational responses to aneuploidy in yeast.

Dephoure N, Hwang S, O'Sullivan C, Dodgson SE, Gygi SP, Amon A, Torres EM - Elife (2014)

APS in the meiotically generated aneuploid strains.(A) Comparison of protein levels of the APS in five aneuploidy strains from Pavelka et al. (2010). Averaged protein (red bars) expression of the APS of each aneuploid strain are shown below. Error bars represent SEM. (B) Correlation of the average APS and chromosome size in five aneuploidy strains from Pavelka et al. (2010). Linear fit is shown in dashed line.DOI:http://dx.doi.org/10.7554/eLife.03023.026
© Copyright Policy - open-access
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4129440&req=5

fig6s2: APS in the meiotically generated aneuploid strains.(A) Comparison of protein levels of the APS in five aneuploidy strains from Pavelka et al. (2010). Averaged protein (red bars) expression of the APS of each aneuploid strain are shown below. Error bars represent SEM. (B) Correlation of the average APS and chromosome size in five aneuploidy strains from Pavelka et al. (2010). Linear fit is shown in dashed line.DOI:http://dx.doi.org/10.7554/eLife.03023.026
Mentions: GO enrichment analysis of the APS revealed a group of proteins associated with cellular responses to oxidative stress, including thioredoxins Trx1 and Trx2, oxidoreductases Grx1 and Grx5, peroxiredoxins Ahp1 and Prx1, and the superoxide dismutase Sod1. In addition, the APS included proteins upregulated during oxidative stress such as the yeast orthologue of the translationally controlled tumor protein (p23) Tma19, the essential NTPase required for ribosome synthesis Fap7, the 3′-5′-exodeoxyribonuclease YBL055C, and the polyamine synthases Spe3 and Spe4 (Gasch et al., 2000; Juhnke et al., 2000; Chattopadhyay et al., 2006). These results indicate that aneuploid cells may be exposed to higher levels of intracellular reactive oxygen species (ROS) (see below). Another GO category of APS-enriched genes is ‘metabolic processes’, including functions such as amino acid biosynthesis and cellular bioenergetics. Interestingly, the intensity of the APS, measured as the average increase of its 92 proteins, correlated with the size of the additional chromosome (Pearson r = 0.62, Figure 6B), indicating that it may be a direct consequence of the cellular imbalances caused by the presence of the extra chromosome, rather than due to increased dosage of specific genes. In addition, we found that the APS is also present in aneuploid strains isolated from random meiosis and that its intensity also correlated with the size of the additional chromosomes in those aneuploid strains (Figure 6—figure supplement 2).

Bottom Line: Our proteomic analyses further revealed a novel aneuploidy-associated protein expression signature characteristic of altered metabolism and redox homeostasis.Interestingly, increased protein turnover attenuates ROS levels and this novel aneuploidy-associated signature and improves the fitness of most aneuploid strains.Our results show that aneuploidy causes alterations in metabolism and redox homeostasis.

View Article: PubMed Central - PubMed

Affiliation: Department of Cell Biology, Harvard Medical School, Boston, United States.

Show MeSH
Related in: MedlinePlus