Protein aggregation mediates stoichiometry of protein complexes in aneuploid cells

Christopher M. Brennan, Laura Pontano Vaites, Jonathan N. Wells, Stefano Santaguida, Joao A. Paulo, Zuzana Storchova, J. Wade Harper, Joseph A. Marsh, Angelika Amon

Research output: Contribution to journalArticlepeer-review

Abstract

Aneuploidy, a condition characterized by chromosome gains and losses, causes reduced fitness and numerous cellular stresses, including increased protein aggregation. Here, we identify protein complex stoichiometry imbalances as a major cause of protein aggregation in aneuploid cells. Subunits of protein complexes encoded on excess chromosomes aggregate in aneuploid cells, which is suppressed when expression of other subunits is coordinately altered. We further show that excess subunits are either degraded or aggregate and that protein aggregation is nearly as effective as protein degradation at lowering levels of excess proteins. Our study explains why proteotoxic stress is a universal feature of the aneuploid state and reveals protein aggregation as a form of dosage compensation to cope with disproportionate expression of protein complex subunits.

Original languageEnglish
Pages (from-to)1031-1047
Number of pages17
JournalGenes and Development
Volume33
Issue number15-16
DOIs
Publication statusPublished - Aug 2019

Keywords

  • Aneuploidy
  • Protein aggregation
  • Protein homeostasis

ASJC Scopus subject areas

  • Genetics
  • Developmental Biology

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