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.
Protein aggregation mediates stoichiometry of protein complexes in aneuploid cells / C.M. Brennan, L.P. Vaites, J.N. Wells, S. Santaguida, J.A. Paulo, Z. Storchova, J.W. Harper, J.A. Marsh, A. Amon. - In: GENES & DEVELOPMENT. - ISSN 0890-9369. - 33:15-16(2019 Aug), pp. 1031-1047.
|Titolo:||Protein aggregation mediates stoichiometry of protein complexes in aneuploid cells|
|Parole Chiave:||Aneuploidy; Protein aggregation; Protein homeostasis; Cytosol; Dosage Compensation, Genetic; Humans; Multiprotein Complexes; Protein Aggregates; Protein Aggregation, Pathological; Protein Subunits; Proteolysis; Saccharomyces cerevisiae; Saccharomyces cerevisiae Proteins; Aneuploidy|
|Settore Scientifico Disciplinare:||Settore BIO/11 - Biologia Molecolare|
|Data di pubblicazione:||ago-2019|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.1101/gad.327494.119|
|Appare nelle tipologie:||01 - Articolo su periodico|