Protein aggregation mediates stoichiometry of protein complexes in aneuploid cells
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 pro...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Cold Spring Harbor Laboratory
2020
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| Online Access: | https://hdl.handle.net/1721.1/125985 |
| _version_ | 1826199465409642496 |
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| author | 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 |
| author2 | Koch Institute for Integrative Cancer Research at MIT |
| author_facet | Koch Institute for Integrative Cancer Research at MIT 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 |
| author_sort | Brennan, Christopher M |
| collection | MIT |
| description | 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. |
| first_indexed | 2024-09-23T11:20:40Z |
| format | Article |
| id | mit-1721.1/125985 |
| institution | Massachusetts Institute of Technology |
| language | English |
| last_indexed | 2024-09-23T11:20:40Z |
| publishDate | 2020 |
| publisher | Cold Spring Harbor Laboratory |
| record_format | dspace |
| spelling | mit-1721.1/1259852022-09-27T18:53:23Z Protein aggregation mediates stoichiometry of protein complexes in aneuploid cells 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 Koch Institute for Integrative Cancer Research at MIT 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. National Institutes of Health (Grant CA206157) National Institutes of Health (Grant GM118066) 2020-06-25T19:24:27Z 2020-06-25T19:24:27Z 2019-06 2019-04 2019-11-26T15:32:23Z Article http://purl.org/eprint/type/JournalArticle 0890-9369 1549-5477 https://hdl.handle.net/1721.1/125985 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 en http://dx.doi.org/10.1101/gad.327494.119 Genes and Development Creative Commons Attribution NonCommercial License 4.0 https://creativecommons.org/licenses/by-nc/4.0/ application/pdf Cold Spring Harbor Laboratory Cold Spring Harbor Laboratory Press |
| spellingShingle | 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 Protein aggregation mediates stoichiometry of protein complexes in aneuploid cells |
| title | Protein aggregation mediates stoichiometry of protein complexes in aneuploid cells |
| title_full | Protein aggregation mediates stoichiometry of protein complexes in aneuploid cells |
| title_fullStr | Protein aggregation mediates stoichiometry of protein complexes in aneuploid cells |
| title_full_unstemmed | Protein aggregation mediates stoichiometry of protein complexes in aneuploid cells |
| title_short | Protein aggregation mediates stoichiometry of protein complexes in aneuploid cells |
| title_sort | protein aggregation mediates stoichiometry of protein complexes in aneuploid cells |
| url | https://hdl.handle.net/1721.1/125985 |
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