Novel alterations in CDK1/cyclin B1 kinase complex formation occur during the acquisition of a polyploid DNA content.
Mol Biol Cell
; 7(2): 209-23, 1996 Feb.
Article
em En
| MEDLINE
| ID: mdl-8688553
ABSTRACT
The pathways that regulate the S-phase events associated with the control of DNA replication are poorly understood. The bone marrow megakaryocytes are unique in that they leave the diploid (2C) state to differentiate, synthesizing 4 to 64 times the normal DNA content within a single nucleus, a process known as endomitosis. Human erythroleukemia (HEL) cells model this process, becoming polyploid during phorbol diester-induced megakaryocyte differentiation. The mitotic arrest occurring in these polyploid cells involves novel alterations in the cdk1/cyclin B1 complex a marked reduction in cdk1 protein levels, and an elevated and sustained expression of cyclin B1. Endomitotic cells thus lack cdk1/cyclin B1-associated H1-histone kinase activity. Constitutive over-expression of cdk1 in endomitotic cells failed to re-initiate normal mitotic events even though cdk1 was present in a 10-fold excess. This was due to an inability of cyclin-B1 to physically associate with cdk1. Nonetheless, endomitotic cyclin B1 possesses immunoprecipitable H1-histone kinase activity, and specifically translocates to the nucleus. We conclude that mitosis is abrogated during endomitosis due to the absence of cdk1 and the failure to form M-phase promoting factor, resulting in a disassociation of mitosis from the completion of S-phase. Further studies on cyclin and its interacting proteins should be informative in understanding endomitosis and cell cycle control.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Poliploidia
/
Proteína Quinase CDC2
/
Ciclinas
/
Ciclina B
Tipo de estudo:
Prognostic_studies
Limite:
Humans
Idioma:
En
Revista:
Mol Biol Cell
Assunto da revista:
BIOLOGIA MOLECULAR
Ano de publicação:
1996
Tipo de documento:
Article
País de afiliação:
Estados Unidos