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Protein aggregation mediates stoichiometry of protein complexes in aneuploid cells

Author(s)
Brennan, Christopher M; Vaites, Laura Pontano; Wells, Jonathan N.; Santaguida, Stefano; Paulo, Joao A.; Storchova, Zuzana; Harper, J. Wade; Marsh, Joseph A.; Amon, Angelika B; ... Show more Show less
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Creative Commons Attribution NonCommercial License 4.0 https://creativecommons.org/licenses/by-nc/4.0/
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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.
Date issued
2019-06
URI
https://hdl.handle.net/1721.1/125985
Department
Koch Institute for Integrative Cancer Research at MIT
Journal
Genes and Development
Publisher
Cold Spring Harbor Laboratory
Citation
Brennan, Christopher M. et al. "Protein aggregation mediates stoichiometry of protein complexes in aneuploid cells." Genes and Development 33, 15-16 (June 2019): 1031-1047 © 2019 The Authors
Version: Final published version
ISSN
0890-9369
1549-5477

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