Protein aggregation mediates stoichiometry of protein complexes in aneuploid cells
Name
Genes Dev.-2019-Brennan-1031-47.pdf
Description
Published version
Size
6.69 MB
Format
Adobe PDF
Checksum (MD5)
68f8657814861a189579ebcb4786a377
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
Date Issued
June 2019
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
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.
MIT Department
Koch Institute for Integrative Cancer Research at MIT
Terms of Use
Creative Commons Attribution NonCommercial License 4.0
Persistent DSpace Link
DOI of Published Version
https://doi.org/10.1101/gad.327494.119
