Cyclin A/Cdk1 modulates Plk1 activity in prometaphase to regulate kinetochore-microtubule attachment stability.
Elife
; 62017 11 20.
Article
em En
| MEDLINE
| ID: mdl-29154753
ABSTRACT
The fidelity of chromosome segregation in mitosis is safeguarded by the precise regulation of kinetochore microtubule (k-MT) attachment stability. Previously, we demonstrated that Cyclin A/Cdk1 destabilizes k-MT attachments to promote faithful chromosome segregation. Here, we use quantitative phosphoproteomics to identify 156 Cyclin A/Cdk1 substrates in prometaphase. One Cyclin A/Cdk1 substrate is myosin phosphatase targeting subunit 1 (MYPT1), and we show that MYPT1 localization to kinetochores depends on Cyclin A/Cdk1 activity and that MYPT1 destabilizes k-MT attachments by negatively regulating Plk1 at kinetochores. Thus, Cyclin A/Cdk1 phosphorylation primes MYPT1 for Plk1 binding. Interestingly, priming of PBIP1 by Plk1 itself (self-priming) increased in MYPT1-depleted cells showing that MYPT1 provides a molecular link between the processes of Cdk1-dependent priming and self-priming of Plk1 substrates. These data demonstrate cross-regulation between Cyclin A/Cdk1-dependent and Plk1-dependent phosphorylation of substrates during mitosis to ensure efficient correction of k-MT attachment errors necessary for high mitotic fidelity.
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Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Proteína Quinase CDC2
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Proteínas Proto-Oncogênicas
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Proteínas Serina-Treonina Quinases
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Cinetocoros
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Proteínas de Ciclo Celular
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Ciclina A
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Fosfatase de Miosina-de-Cadeia-Leve
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Prometáfase
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Microtúbulos
Idioma:
En
Ano de publicação:
2017
Tipo de documento:
Article