Cell Calcium, volume 88, pages 102207

The impact of calmodulin on the cell cycle analyzed in a novel human cellular genetic system

Mads Munk 1
Juan Alcalde 2, 3
Lasse Lorentzen 4
Antonio VILLALOBO 5
MARTIN W. BERCHTOLD 1
Svetlana Panina 3
Publication typeJournal Article
Publication date2020-06-01
Journal: Cell Calcium
scimago Q1
SJR1.309
CiteScore8.7
Impact factor4.3
ISSN01434160, 15321991
Molecular Biology
Cell Biology
Physiology
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 120 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 β-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.

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