Robust mitotic entry is ensured by a latching switch
Summary Cell cycle events are driven by Cyclin dependent kinases (CDKs) and by their counter-acting phosphatases. Activation of the Cdk1:Cyclin B complex during mitotic entry is controlled by the Wee1/Myt1 inhibitory kinases and by Cdc25 activatory phosphatase, which are themselves regulated by Cdk1...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
The Company of Biologists
2013-07-01
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| Series: | Biology Open |
| Subjects: | |
| Online Access: | http://bio.biologists.org/content/2/9/924 |
| _version_ | 1830302910785781760 |
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| author | Chloe Tuck Tongli Zhang Tamara Potapova Marcos Malumbres Béla Novák |
| author_facet | Chloe Tuck Tongli Zhang Tamara Potapova Marcos Malumbres Béla Novák |
| author_sort | Chloe Tuck |
| collection | DOAJ |
| description | Summary
Cell cycle events are driven by Cyclin dependent kinases (CDKs) and by their counter-acting phosphatases. Activation of the Cdk1:Cyclin B complex during mitotic entry is controlled by the Wee1/Myt1 inhibitory kinases and by Cdc25 activatory phosphatase, which are themselves regulated by Cdk1:Cyclin B within two positive circuits. Impairing these two feedbacks with chemical inhibitors induces a transient entry into M phase referred to as mitotic collapse. The pathology of mitotic collapse reveals that the positive circuits play a significant role in maintaining the M phase state. To better understand the function of these feedback loops during G2/M transition, we propose a simple model for mitotic entry in mammalian cells including spatial control over Greatwall kinase phosphorylation. After parameter calibration, the model is able to recapture the complex and non-intuitive molecular dynamics reported by Potapova et al. (Potapova et al., 2011). Moreover, it predicts the temporal patterns of other mitotic regulators which have not yet been experimentally tested and suggests a general design principle of cell cycle control: latching switches buffer the cellular stresses which accompany cell cycle processes to ensure that the transitions are smooth and robust. |
| first_indexed | 2024-12-19T09:15:52Z |
| format | Article |
| id | doaj.art-39fb67d5cf8d440caf4fa0be1d0e300d |
| institution | Directory Open Access Journal |
| issn | 2046-6390 |
| language | English |
| last_indexed | 2024-12-19T09:15:52Z |
| publishDate | 2013-07-01 |
| publisher | The Company of Biologists |
| record_format | Article |
| series | Biology Open |
| spelling | doaj.art-39fb67d5cf8d440caf4fa0be1d0e300d2022-12-21T20:28:05ZengThe Company of BiologistsBiology Open2046-63902013-07-012992493110.1242/bio.2013519920135199Robust mitotic entry is ensured by a latching switchChloe Tuck0Tongli Zhang1Tamara Potapova2Marcos Malumbres3Béla Novák4 Oxford Centre for Integrative Systems Biology, Department of Biochemistry, South Parks Road, Oxford OX1 3QU, UK Oxford Centre for Integrative Systems Biology, Department of Biochemistry, South Parks Road, Oxford OX1 3QU, UK Stowers Institute for Medical Research, Kansas City, MO 64110, USA Cell Division and Cancer Group, Spanish National Cancer Research Centre (CNIO), Melchor Fernández Almagro 3, E-28029 Madrid, Spain Oxford Centre for Integrative Systems Biology, Department of Biochemistry, South Parks Road, Oxford OX1 3QU, UK Summary Cell cycle events are driven by Cyclin dependent kinases (CDKs) and by their counter-acting phosphatases. Activation of the Cdk1:Cyclin B complex during mitotic entry is controlled by the Wee1/Myt1 inhibitory kinases and by Cdc25 activatory phosphatase, which are themselves regulated by Cdk1:Cyclin B within two positive circuits. Impairing these two feedbacks with chemical inhibitors induces a transient entry into M phase referred to as mitotic collapse. The pathology of mitotic collapse reveals that the positive circuits play a significant role in maintaining the M phase state. To better understand the function of these feedback loops during G2/M transition, we propose a simple model for mitotic entry in mammalian cells including spatial control over Greatwall kinase phosphorylation. After parameter calibration, the model is able to recapture the complex and non-intuitive molecular dynamics reported by Potapova et al. (Potapova et al., 2011). Moreover, it predicts the temporal patterns of other mitotic regulators which have not yet been experimentally tested and suggests a general design principle of cell cycle control: latching switches buffer the cellular stresses which accompany cell cycle processes to ensure that the transitions are smooth and robust.http://bio.biologists.org/content/2/9/924G2/M transitionMitotic entryMitotic collapseGreatwall kinaseSpatial control of mitosisCell cycle |
| spellingShingle | Chloe Tuck Tongli Zhang Tamara Potapova Marcos Malumbres Béla Novák Robust mitotic entry is ensured by a latching switch Biology Open G2/M transition Mitotic entry Mitotic collapse Greatwall kinase Spatial control of mitosis Cell cycle |
| title | Robust mitotic entry is ensured by a latching switch |
| title_full | Robust mitotic entry is ensured by a latching switch |
| title_fullStr | Robust mitotic entry is ensured by a latching switch |
| title_full_unstemmed | Robust mitotic entry is ensured by a latching switch |
| title_short | Robust mitotic entry is ensured by a latching switch |
| title_sort | robust mitotic entry is ensured by a latching switch |
| topic | G2/M transition Mitotic entry Mitotic collapse Greatwall kinase Spatial control of mitosis Cell cycle |
| url | http://bio.biologists.org/content/2/9/924 |
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