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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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Ribosome and proteasome levels in aneuploid cells.(A) Averaged protein levels of proteasome subunits of each disomic strain relative to wild-type cells grown in synthetic (top) or YEPD (bottom) medium. Error bars represent SEM. (B) Averaged protein levels of ribosome subunits of each disomic strain relative to wild-type cells grown in synthetic (top) or YEPD (bottom) medium. Error bars represent SEM.DOI:http://dx.doi.org/10.7554/eLife.03023.027
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fig6s3: Ribosome and proteasome levels in aneuploid cells.(A) Averaged protein levels of proteasome subunits of each disomic strain relative to wild-type cells grown in synthetic (top) or YEPD (bottom) medium. Error bars represent SEM. (B) Averaged protein levels of ribosome subunits of each disomic strain relative to wild-type cells grown in synthetic (top) or YEPD (bottom) medium. Error bars represent SEM.DOI:http://dx.doi.org/10.7554/eLife.03023.027

Mentions: Despite not finding a statistically significant enrichment for cellular processes associated with proteotoxic stress, we found several upregulated proteins involved in protein quality control pathways (Figure 6—source data 1). These include the Hsp90 regulators Sba1 and Hch1, the cis-trans peptide isomerases Cpr3, Fpr1 and Fpr3, and three proteins involved in ubiquitination including the ubiquitin-conjugating enzyme Ubc1, the ubiquitin interacting protein Duf1 and the ubiquitin-like protein Rub1. In addition, APS genes included several proteins involved in protein trafficking including Arc1, Sec53, Ric1, Vti1 and Ykt6. The upregulation of these proteins is consistent with increases in flux through protein folding, trafficking, and turnover machinery in aneuploid cells and will form the basis for future investigations. In support of a proposed need for increased protein degradation, we found that the average levels of proteasome subunits in all the disomic strains showed a small but significant increase compared to wild-type cells in almost every disomic strain independent of growth conditions (Figure 6—figure supplement 3).


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)

Ribosome and proteasome levels in aneuploid cells.(A) Averaged protein levels of proteasome subunits of each disomic strain relative to wild-type cells grown in synthetic (top) or YEPD (bottom) medium. Error bars represent SEM. (B) Averaged protein levels of ribosome subunits of each disomic strain relative to wild-type cells grown in synthetic (top) or YEPD (bottom) medium. Error bars represent SEM.DOI:http://dx.doi.org/10.7554/eLife.03023.027
© Copyright Policy - open-access
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4129440&req=5

fig6s3: Ribosome and proteasome levels in aneuploid cells.(A) Averaged protein levels of proteasome subunits of each disomic strain relative to wild-type cells grown in synthetic (top) or YEPD (bottom) medium. Error bars represent SEM. (B) Averaged protein levels of ribosome subunits of each disomic strain relative to wild-type cells grown in synthetic (top) or YEPD (bottom) medium. Error bars represent SEM.DOI:http://dx.doi.org/10.7554/eLife.03023.027
Mentions: Despite not finding a statistically significant enrichment for cellular processes associated with proteotoxic stress, we found several upregulated proteins involved in protein quality control pathways (Figure 6—source data 1). These include the Hsp90 regulators Sba1 and Hch1, the cis-trans peptide isomerases Cpr3, Fpr1 and Fpr3, and three proteins involved in ubiquitination including the ubiquitin-conjugating enzyme Ubc1, the ubiquitin interacting protein Duf1 and the ubiquitin-like protein Rub1. In addition, APS genes included several proteins involved in protein trafficking including Arc1, Sec53, Ric1, Vti1 and Ykt6. The upregulation of these proteins is consistent with increases in flux through protein folding, trafficking, and turnover machinery in aneuploid cells and will form the basis for future investigations. In support of a proposed need for increased protein degradation, we found that the average levels of proteasome subunits in all the disomic strains showed a small but significant increase compared to wild-type cells in almost every disomic strain independent of growth conditions (Figure 6—figure supplement 3).

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