The impact of calmodulin on the cell cycle analyzed in a novel human cellular genetic system.
Cell Calcium
; 88: 102207, 2020 06.
Article
em En
| MEDLINE
| ID: mdl-32408024
ABSTRACT
Calmodulin (CaM) is the principle mediator of the Ca2+ signal in all eukaryotic cells. A huge variety of basic cellular processes including cell cycle control, proliferation, secretion and motility, among many others are governed by CaM, which regulates activities of myriads of target proteins. Mammalian CaM is encoded by three genes localized on different chromosomes all producing an identical protein. In this study, we have generated HeLa human cancer cells conditionally expressing CaM in a genetic background with all three genes inactivated by CRISPR/Cas9. We demonstrate that downregulation of ectopically expressed CaM is achieved after 120â¯h, when cells are arrested in the M phase of the cell cycle. We show for the first time that CaM downregulation in human cancer cells is followed by a multinucleated senescent state as indicated by expression of ß-galactosidase as well as cell morphology typical for senescent cells. Our newly generated genetic system may be useful for the analysis of other CaM regulated processes in eukaryotic cells in the absence of endogenous CaM genes.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Calmodulina
/
Ciclo Celular
/
Células
Limite:
Humans
Idioma:
En
Revista:
Cell Calcium
Ano de publicação:
2020
Tipo de documento:
Article
País de afiliação:
Dinamarca