Proteomics

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Protein aggregation mediates protein complex stoichiometry in aneuploid cells, part 3


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.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Saccharomyces Cerevisiae (baker's Yeast)

SUBMITTER: Laura Vaites  

LAB HEAD: Angelika Amon

PROVIDER: PXD011876 | Pride | 2020-05-26

REPOSITORIES: Pride

Dataset's files

Source:
Action DRS
291437_231.1_j30037.mzIdentML Mzid
291438_231.1_j30038.mzIdentML Mzid
291439_231.1_j30039.mzIdentML Mzid
291440_231.1_j30040.mzIdentML Mzid
291441_231.2_j30042.mzIdentML Mzid
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Publications

Protein aggregation mediates stoichiometry of protein complexes in aneuploid cells.

Brennan Christopher M CM   Vaites Laura Pontano LP   Wells Jonathan N JN   Santaguida Stefano S   Paulo Joao A JA   Storchova Zuzana Z   Harper J Wade JW   Marsh Joseph A JA   Amon Angelika A  

Genes & development 20190613 15-16


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 eithe  ...[more]

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