CDK1-CCNB1 creates a spindle checkpoint-permissive state by enabling MPS1 kinetochore localization.
J Cell Biol
; 218(4): 1182-1199, 2019 04 01.
Article
em En
| MEDLINE
| ID: mdl-30674582
ABSTRACT
Spindle checkpoint signaling is initiated by recruitment of the kinase MPS1 to unattached kinetochores during mitosis. We show that CDK1-CCNB1 and a counteracting phosphatase PP2A-B55 regulate the engagement of human MPS1 with unattached kinetochores by controlling the phosphorylation status of S281 in the kinetochore-binding domain. This regulation is essential for checkpoint signaling, since MPS1S281A is not recruited to unattached kinetochores and fails to support the recruitment of other checkpoint proteins. Directly tethering MPS1S281A to the kinetochore protein Mis12 bypasses this regulation and hence the requirement for S281 phosphorylation in checkpoint signaling. At the metaphase-anaphase transition, MPS1 S281 dephosphorylation is delayed because PP2A-B55 is negatively regulated by CDK1-CCNB1 and only becomes fully active once CCNB1 concentration falls below a characteristic threshold. This mechanism prolongs the checkpoint-responsive period when MPS1 can localize to kinetochores and enables a response to late-stage spindle defects. By acting together, CDK1-CCNB1 and PP2A-B55 thus create a spindle checkpoint-permissive state and ensure the fidelity of mitosis.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Proteínas Tirosina Quinases
/
Núcleo Celular
/
Proteína Quinase CDC2
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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 B1
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Pontos de Checagem da Fase M do Ciclo Celular
Limite:
Humans
Idioma:
En
Revista:
J Cell Biol
Ano de publicação:
2019
Tipo de documento:
Article