Deletion of INMAP postpones mitotic exit and induces apoptosis by disabling the formation of mitotic spindle.
Biochem Biophys Res Commun
; 518(1): 19-25, 2019 10 08.
Article
em En
| MEDLINE
| ID: mdl-31405563
ABSTRACT
INMAP was first identified as a spindle protein that plays important roles in cell-cycle progression, and previous studies have revealed that its abnormal expression leads to mitotic disorder and the growth inhibition of human tumor xenografts, but the underlying mechanism is still unclear. In this study, we knocked out INMAP in HEK293T cells, a strain of human embryonic renal cells, through CRISPR-Cas9 gene editing technology, resulting in obvious cell growth inhibition. In this system, the deletion of INMAP caused obviously apoptosis. And we also found that knockout of INMAP caused micronuclei formation, chromosome aberration, and γH2AX expression upregulation, suggesting DNA damage induction and genomic stability impairment. As a principal component of spindle, the expression of ß-tubulin, detected through Western blot, is obviously upregulated in HEK293T-INMAP-/-. Meanwhile, the level of Cyclin B is also upregulated, whereas, that of Cyclin E, downregulated, with the postponement of mitotic exit and the assembly anomaly of spindle. These results suggest that the deletion of INMAP block the formation of spindle, leading to arrest of cell cycle and DNA damage, finally blocking cell proliferation and inducing apoptosis. Therefore, INMAP is an indispensable factor for genomic integrity and normal mitotic exit.
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Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Proteínas Nucleares
/
Deleção de Genes
/
Apoptose
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Proteínas de Ciclo Celular
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Mitose
/
Fuso Acromático
Tipo de estudo:
Prognostic_studies
Limite:
Humans
Idioma:
En
Revista:
Biochem Biophys Res Commun
Ano de publicação:
2019
Tipo de documento:
Article