Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 2 de 2
Filtrar
Más filtros










Base de datos
Tipo de estudio
Intervalo de año de publicación
1.
J Cell Sci ; 134(1)2021 01 08.
Artículo en Inglés | MEDLINE | ID: mdl-33288550

RESUMEN

Errors in mitotic chromosome segregation can lead to DNA damage and aneuploidy, both hallmarks of cancer. To achieve synchronous error-free segregation, mitotic chromosomes must align at the metaphase plate with stable amphitelic attachments to microtubules emanating from opposing spindle poles. The astrin-kinastrin (astrin is also known as SPAG5 and kinastrin as SKAP) complex, also containing DYNLL1 and MYCBP, is a spindle and kinetochore protein complex with important roles in bipolar spindle formation, chromosome alignment and microtubule-kinetochore attachment. However, the molecular mechanisms by which astrin-kinastrin fulfils these diverse roles are not fully understood. Here, we characterise a direct interaction between astrin and the mitotic kinase Plk1. We identify the Plk1-binding site on astrin as well as four Plk1 phosphorylation sites on astrin. Regulation of astrin by Plk1 is dispensable for bipolar spindle formation and bulk chromosome congression, but promotes stable microtubule-kinetochore attachments and metaphase plate maintenance. It is known that Plk1 activity is required for effective microtubule-kinetochore attachment formation, and we suggest that astrin phosphorylation by Plk1 contributes to this process.


Asunto(s)
Proteínas de Ciclo Celular , Proteínas Asociadas a Microtúbulos , Azul Alcián , Proteínas de Ciclo Celular/genética , Segregación Cromosómica , Células HeLa , Humanos , Cinetocoros , Metafase , Proteínas Asociadas a Microtúbulos/genética , Microtúbulos , Mitosis , Fenazinas , Fenotiazinas , Proteínas Serina-Treonina Quinasas , Proteínas Proto-Oncogénicas , Resorcinoles , Huso Acromático/genética , Quinasa Tipo Polo 1
2.
Mol Biol Cell ; 31(21): 2315-2330, 2020 10 01.
Artículo en Inglés | MEDLINE | ID: mdl-32755477

RESUMEN

Ubiquitin-dependent proteolysis of cyclin B and securin initiates sister chromatid segregation and anaphase. The anaphase-promoting complex/cyclosome and its coactivator CDC20 (APC/CCDC20) form the main ubiquitin E3 ligase for these two proteins. APC/CCDC20 is regulated by CDK1-cyclin B and counteracting PP1 and PP2A family phosphatases through modulation of both activating and inhibitory phosphorylation. Here, we report that PP1 promotes cyclin B destruction at the onset of anaphase by removing specific inhibitory phosphorylation in the N-terminus of CDC20. Depletion or chemical inhibition of PP1 stabilizes cyclin B and results in a pronounced delay at the metaphase-to-anaphase transition after chromosome alignment. This requirement for PP1 is lost in cells expressing CDK1 phosphorylation-defective CDC206A mutants. These CDC206A cells show a normal spindle checkpoint response and rapidly destroy cyclin B once all chromosomes have aligned and enter into anaphase in the absence of PP1 activity. PP1 therefore facilitates the metaphase-to-anaphase transition by promoting APC/CCDC20-dependent destruction of cyclin B in human cells.


Asunto(s)
Proteínas Cdc20/metabolismo , Segregación Cromosómica , Ciclina B/metabolismo , Receptores de Neuropéptido Y/metabolismo , Anafase , Células HeLa , Humanos , Metafase , Fosforilación , Procesamiento Proteico-Postraduccional , Proteolisis
SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA
...