Quantitative proteomic analysis reveals posttranslational responses to aneuploidy in yeast

  1. Noah Dephoure
  2. Sunyoung Hwang
  3. Ciara O'Sullivan
  4. Stacie E Dodgson
  5. Steve P Gygi
  6. Angelika Amon
  7. Eduardo M Torres  Is a corresponding author
  1. Harvard Medical School, United States
  2. University of Massachusetts Medical School, United States
  3. Massachusetts Institute of Technology, United States

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.

Article and author information

Author details

  1. Noah Dephoure

    Harvard Medical School, Boston, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Sunyoung Hwang

    University of Massachusetts Medical School, Worcester, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Ciara O'Sullivan

    University of Massachusetts Medical School, Worcester, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Stacie E Dodgson

    Massachusetts Institute of Technology, Cambridge, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Steve P Gygi

    Harvard Medical School, Boston, United States
    Competing interests
    The authors declare that no competing interests exist.
  6. Angelika Amon

    Massachusetts Institute of Technology, Cambridge, United States
    Competing interests
    The authors declare that no competing interests exist.
  7. Eduardo M Torres

    University of Massachusetts Medical School, Worcester, United States
    For correspondence
    eduardo.torres@umassmed.edu
    Competing interests
    The authors declare that no competing interests exist.

Reviewing Editor

  1. Ivan Dikic, Goethe University, Germany

Publication history

  1. Received: April 6, 2014
  2. Accepted: July 27, 2014
  3. Accepted Manuscript published: July 29, 2014 (version 1)
  4. Accepted Manuscript updated: July 30, 2014 (version 2)
  5. Version of Record published: August 12, 2014 (version 3)

Copyright

© 2014, Dephoure et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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  1. Noah Dephoure
  2. Sunyoung Hwang
  3. Ciara O'Sullivan
  4. Stacie E Dodgson
  5. Steve P Gygi
  6. Angelika Amon
  7. Eduardo M Torres
(2014)
Quantitative proteomic analysis reveals posttranslational responses to aneuploidy in yeast
eLife 3:e03023.
https://doi.org/10.7554/eLife.03023

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