Author:
Brennan Christopher M.,Vaites Laura Pontano,Wells Jonathan N.,Santaguida Stefano,Paulo Joao A.,Storchova Zuzana,Harper J. Wade,Marsh Joseph A.,Amon Angelika
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.
Funder
National Institutes of Health
Medical Research Council Career Development Award
American Italian Cancer Foundation
Marie Curie Actions
Italian Association for Cancer Research
Koch Institute Quinquennial Cancer Research Fellowship
Publisher
Cold Spring Harbor Laboratory
Subject
Developmental Biology,Genetics
Cited by
93 articles.
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