title: Quantitative proteomic analysis reveals posttranslational responses to aneuploidy in yeast.
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.
authors: Department of Cell Biology, Harvard Medical School, Boston, United States.
authors: Noah
authors: N
authors: Dephoure
authors: Program in Gene Function and Expression, University of Massachusetts Medical School, Worcester, United States.
authors: Sunyoung
authors: S
authors: Hwang
authors: Program in Gene Function and Expression, University of Massachusetts Medical School, Worcester, United States.
authors: Ciara
authors: C
authors: O'Sullivan
authors: David H. Koch Institute for Integrative Cancer Research, Howard Hughes Medical Institute, Massachusetts Institute of Technology, Cambridge, United States.
authors: Stacie E
authors: SE
authors: Dodgson
authors: Department of Cell Biology, Harvard Medical School, Boston, United States.
authors: Steven P
authors: SP
authors: Gygi
authors: David H. Koch Institute for Integrative Cancer Research, Howard Hughes Medical Institute, Massachusetts Institute of Technology, Cambridge, United States.
authors: Angelika
authors: A
authors: Amon
authors: Program in Gene Function and Expression, University of Massachusetts Medical School, Worcester, United States eduardo.torres@umassmed.edu.
authors: Eduardo M
authors: EM
authors: Torres
mesh_terms: D000782:Aneuploidy; D018628:Gene Dosage; D015966:Gene Expression Regulation, Fungal; D053858:Metabolic Networks and Pathways; D010084:Oxidation-Reduction; D011499:Protein Processing, Post-Translational; D040901:Proteomics; D017382:Reactive Oxygen Species / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000235:genetics* / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics* / Q000378:metabolism; D014158:Transcription, Genetic; D059467:Transcriptome
chemical_list: D017382:Reactive Oxygen Species; D029701:Saccharomyces cerevisiae Proteins
keywords: aneuploidy; posttranscriptional mechanisms; posttranslational mechanisms; proteomics