MAD1-dependent recruitment of CDK1-CCNB1 to kinetochores promotes spindle checkpoint signaling
Cyclin B–dependent kinase (CDK1-CCNB1) promotes entry into mitosis. Additionally, it inhibits mitotic exit by activating the spindle checkpoint. This latter role is mediated through phosphorylation of the checkpoint kinase MPS1 and other spindle checkpoint proteins. We find that CDK1-CCNB1 localizes...
| Main Authors: | , , , , |
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| Format: | Journal article |
| Sprog: | English |
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Rockefeller University Press
2019
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| _version_ | 1826270842149928960 |
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| author | Alfonso-Pérez, T Hayward, D Holder, J Gruneberg, U Barr, F |
| author_facet | Alfonso-Pérez, T Hayward, D Holder, J Gruneberg, U Barr, F |
| author_sort | Alfonso-Pérez, T |
| collection | OXFORD |
| description | Cyclin B–dependent kinase (CDK1-CCNB1) promotes entry into mitosis. Additionally, it inhibits mitotic exit by activating the spindle checkpoint. This latter role is mediated through phosphorylation of the checkpoint kinase MPS1 and other spindle checkpoint proteins. We find that CDK1-CCNB1 localizes to unattached kinetochores and like MPS1 is lost from these structures upon microtubule attachment. This suggests that CDK1-CCNB1 is an integral component and not only an upstream regulator of the spindle checkpoint pathway. Complementary proteomic and cell biological analysis demonstrate that the spindle checkpoint protein MAD1 is one of the major components of CCNB1 complexes, and that CCNB1 is recruited to unattached kinetochores in an MPS1-dependent fashion through interaction with the first 100 amino acids of MAD1. This MPS1 and MAD1-dependent pool of CDK1-CCNB1 creates a positive feedback loop necessary for timely recruitment of MPS1 to kinetochores during mitotic entry and for sustained spindle checkpoint arrest. CDK1-CCNB1 is therefore an integral component of the spindle checkpoint, ensuring the fidelity of mitosis. |
| first_indexed | 2024-03-06T21:47:10Z |
| format | Journal article |
| id | oxford-uuid:4a009805-6199-44ba-95c5-896575fbe220 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T21:47:10Z |
| publishDate | 2019 |
| publisher | Rockefeller University Press |
| record_format | dspace |
| spelling | oxford-uuid:4a009805-6199-44ba-95c5-896575fbe2202022-03-26T15:35:05ZMAD1-dependent recruitment of CDK1-CCNB1 to kinetochores promotes spindle checkpoint signalingJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:4a009805-6199-44ba-95c5-896575fbe220EnglishSymplectic Elements at OxfordRockefeller University Press2019Alfonso-Pérez, THayward, DHolder, JGruneberg, UBarr, FCyclin B–dependent kinase (CDK1-CCNB1) promotes entry into mitosis. Additionally, it inhibits mitotic exit by activating the spindle checkpoint. This latter role is mediated through phosphorylation of the checkpoint kinase MPS1 and other spindle checkpoint proteins. We find that CDK1-CCNB1 localizes to unattached kinetochores and like MPS1 is lost from these structures upon microtubule attachment. This suggests that CDK1-CCNB1 is an integral component and not only an upstream regulator of the spindle checkpoint pathway. Complementary proteomic and cell biological analysis demonstrate that the spindle checkpoint protein MAD1 is one of the major components of CCNB1 complexes, and that CCNB1 is recruited to unattached kinetochores in an MPS1-dependent fashion through interaction with the first 100 amino acids of MAD1. This MPS1 and MAD1-dependent pool of CDK1-CCNB1 creates a positive feedback loop necessary for timely recruitment of MPS1 to kinetochores during mitotic entry and for sustained spindle checkpoint arrest. CDK1-CCNB1 is therefore an integral component of the spindle checkpoint, ensuring the fidelity of mitosis. |
| spellingShingle | Alfonso-Pérez, T Hayward, D Holder, J Gruneberg, U Barr, F MAD1-dependent recruitment of CDK1-CCNB1 to kinetochores promotes spindle checkpoint signaling |
| title | MAD1-dependent recruitment of CDK1-CCNB1 to kinetochores promotes spindle checkpoint signaling |
| title_full | MAD1-dependent recruitment of CDK1-CCNB1 to kinetochores promotes spindle checkpoint signaling |
| title_fullStr | MAD1-dependent recruitment of CDK1-CCNB1 to kinetochores promotes spindle checkpoint signaling |
| title_full_unstemmed | MAD1-dependent recruitment of CDK1-CCNB1 to kinetochores promotes spindle checkpoint signaling |
| title_short | MAD1-dependent recruitment of CDK1-CCNB1 to kinetochores promotes spindle checkpoint signaling |
| title_sort | mad1 dependent recruitment of cdk1 ccnb1 to kinetochores promotes spindle checkpoint signaling |
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