Quantitative proteomic analysis reveals posttranslational responses to aneuploidy in yeast
Author(s)
Dephoure, Noah; Hwang, Sunyoung; O'Sullivan, Ciara; Gygi, Steven P; Torres, Eduardo M; Dodgson, Stacie Elizabeth; Amon, Angelika B.; ... Show more Show less
Downloadelife-03023-v3.pdf (6.636Mb)
PUBLISHER_CC
Publisher with Creative Commons License
Creative Commons Attribution
Terms of use
Metadata
Show full item recordAbstract
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.
Date issued
2014-07Department
Koch Institute for Integrative Cancer Research at MITJournal
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
ISSN
2050-084X