Protein aggregation mediates stoichiometry of protein complexes in aneuploid cells
| Autor: | J. Wade Harper, Zuzana Storchova, Angelika Amon, Joao A. Paulo, Jonathan N. Wells, Stefano Santaguida, Laura Pontano Vaites, Joseph A. Marsh, Christopher M. Brennan |
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| Rok vydání: | 2019 |
| Předmět: |
0303 health sciences
Dosage compensation Aneuploidy Chromosome Protein degradation Protein Homeostasis Protein aggregation Biology medicine.disease Cell biology 03 medical and health sciences 0302 clinical medicine 030220 oncology & carcinogenesis Genetics medicine Aneuploid Cells Stoichiometry Research Paper 030304 developmental biology Developmental Biology |
| Zdroj: | Brennan, C M, Vaites, L P, Wells, J N, Santaguida, S, Paulo, J A, Storchova, Z, Harper, J W, Marsh, J A & Amon, A 2019, ' Protein aggregation mediates stoichiometry of protein complexes in aneuploid cells ', Genes and Development, vol. 33, no. 15-16, pp. 1031-1047 . https://doi.org/10.1101/gad.327494.119 |
| ISSN: | 1549-5477 0890-9369 |
| DOI: | 10.1101/gad.327494.119 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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