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Cell-cycle transitions: a common role for stoichiometric inhibitors
The cell division cycle is the process by which eukaryotic cells replicate their chromosomes and partition them to two daughter cells. To maintain the integrity of the genome, proliferating cells must be able to block progression through the division cycle at key transition points (called “checkpoin...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The American Society for Cell Biology
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5687042/ https://www.ncbi.nlm.nih.gov/pubmed/28931595 http://dx.doi.org/10.1091/mbc.E17-06-0349 |
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author | Hopkins, Michael Tyson, John J. Novák, Béla |
author_facet | Hopkins, Michael Tyson, John J. Novák, Béla |
author_sort | Hopkins, Michael |
collection | PubMed |
description | The cell division cycle is the process by which eukaryotic cells replicate their chromosomes and partition them to two daughter cells. To maintain the integrity of the genome, proliferating cells must be able to block progression through the division cycle at key transition points (called “checkpoints”) if there have been problems in the replication of the chromosomes or their biorientation on the mitotic spindle. These checkpoints are governed by protein-interaction networks, composed of phase-specific cell-cycle activators and inhibitors. Examples include Cdk1:Clb5 and its inhibitor Sic1 at the G1/S checkpoint in budding yeast, APC:Cdc20 and its inhibitor MCC at the mitotic checkpoint, and PP2A:B55 and its inhibitor, alpha-endosulfine, at the mitotic-exit checkpoint. Each of these inhibitors is a substrate as well as a stoichiometric inhibitor of the cell-cycle activator. Because the production of each inhibitor is promoted by a regulatory protein that is itself inhibited by the cell-cycle activator, their interaction network presents a regulatory motif characteristic of a “feedback-amplified domineering substrate” (FADS). We describe how the FADS motif responds to signals in the manner of a bistable toggle switch, and then we discuss how this toggle switch accounts for the abrupt and irreversible nature of three specific cell-cycle checkpoints. |
format | Online Article Text |
id | pubmed-5687042 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | The American Society for Cell Biology |
record_format | MEDLINE/PubMed |
spelling | pubmed-56870422018-01-22 Cell-cycle transitions: a common role for stoichiometric inhibitors Hopkins, Michael Tyson, John J. Novák, Béla Mol Biol Cell Articles The cell division cycle is the process by which eukaryotic cells replicate their chromosomes and partition them to two daughter cells. To maintain the integrity of the genome, proliferating cells must be able to block progression through the division cycle at key transition points (called “checkpoints”) if there have been problems in the replication of the chromosomes or their biorientation on the mitotic spindle. These checkpoints are governed by protein-interaction networks, composed of phase-specific cell-cycle activators and inhibitors. Examples include Cdk1:Clb5 and its inhibitor Sic1 at the G1/S checkpoint in budding yeast, APC:Cdc20 and its inhibitor MCC at the mitotic checkpoint, and PP2A:B55 and its inhibitor, alpha-endosulfine, at the mitotic-exit checkpoint. Each of these inhibitors is a substrate as well as a stoichiometric inhibitor of the cell-cycle activator. Because the production of each inhibitor is promoted by a regulatory protein that is itself inhibited by the cell-cycle activator, their interaction network presents a regulatory motif characteristic of a “feedback-amplified domineering substrate” (FADS). We describe how the FADS motif responds to signals in the manner of a bistable toggle switch, and then we discuss how this toggle switch accounts for the abrupt and irreversible nature of three specific cell-cycle checkpoints. The American Society for Cell Biology 2017-11-07 /pmc/articles/PMC5687042/ /pubmed/28931595 http://dx.doi.org/10.1091/mbc.E17-06-0349 Text en © 2017 Hopkins et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0). “ASCB®,” “The American Society for Cell Biology®,” and “Molecular Biology of the Cell®” are registered trademarks of The American Society for Cell Biology. |
spellingShingle | Articles Hopkins, Michael Tyson, John J. Novák, Béla Cell-cycle transitions: a common role for stoichiometric inhibitors |
title | Cell-cycle transitions: a common role for stoichiometric inhibitors |
title_full | Cell-cycle transitions: a common role for stoichiometric inhibitors |
title_fullStr | Cell-cycle transitions: a common role for stoichiometric inhibitors |
title_full_unstemmed | Cell-cycle transitions: a common role for stoichiometric inhibitors |
title_short | Cell-cycle transitions: a common role for stoichiometric inhibitors |
title_sort | cell-cycle transitions: a common role for stoichiometric inhibitors |
topic | Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5687042/ https://www.ncbi.nlm.nih.gov/pubmed/28931595 http://dx.doi.org/10.1091/mbc.E17-06-0349 |
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