Quantitative proteomic analysis reveals posttranslational responses to aneuploidy in yeast
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elife-03023-v3.pdf
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6.64 MB
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Adobe PDF
Checksum (MD5)
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Author(s)
Dephoure, Noah
Hwang, Sunyoung
O'Sullivan, Ciara
Gygi, Steven P
Torres, Eduardo M
Dodgson, Stacie Elizabeth
Amon, Angelika B.
Date Issued
July 2014
Journal
eLife
Publisher
eLife Sciences Organisation, Ltd.
Citation
Dephoure, Noah et al. “Quantitative Proteomic Analysis Reveals Posttranslational Responses to Aneuploidy in Yeast.” eLife 2014, 3 (July 2014): e03023 © Dephoure et al
Version
Final published version
Abstract
Aneuploidy causes severe developmental defects and is a near universal feature of tumor cells. Despite its profound effects, the cellular processes affected by aneuploidy are not well characterized. Here, we examined the consequences of aneuploidy on the proteome of aneuploid budding yeast strains. We show that although protein levels largely scale with gene copy number, subunits of multi-protein complexes are notable exceptions. Posttranslational mechanisms attenuate their expression when their encoding genes are in excess. Our proteomic analyses further revealed a novel aneuploidy-associated protein expression signature characteristic of altered metabolism and redox homeostasis. Indeed aneuploid cells harbor increased levels of reactive oxygen species (ROS). 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. Cells respond to these alterations through both transcriptional and posttranscriptional mechanisms.
MIT Department
Koch Institute for Integrative Cancer Research at MIT
Terms of Use
Creative Commons Attribution 4.0 International License
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DOI of Published Version
https://doi.org/10.7554/ELIFE.03023
