Strong inducible knockdown of APC/CCdc20 does not cause mitotic arrest in human somatic cells

The anaphase-promoting complex/cyclosome (APC/C) is a conserved ubiquitin ligase controlling mitosis and G1 phase of the cell cycle. The APC/C is activated by two regulatory subunits Cdc20 (APC/CCdc20) and Cdh1 (APC/CCdh1) to target securin, mitotic cyclins and other cell cycle regulatory proteins....

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Bibliographic Details
Published in:Cell cycle (Georgetown, Tex.) Tex.), 2009-02, Vol.8 (4), p.643-646
Main Authors: Baumgarten, Axel J., Felthaus, Julia, Wäsch, Ralph
Format: Article
Language:English
Subjects:
Anaphase-Promoting Complex-Cyclosome
Animals
Binding
Biology
Bioscience
Calcium
Cancer
Cdc20 Proteins
Cell
Cell Cycle - physiology
Cell Cycle Proteins - genetics
Cell Cycle Proteins - metabolism
Cycle
Cyclin B - genetics
Cyclin B - metabolism
Gene Knockdown Techniques
Genes, cdc
Humans
Landes
Mice
Mitosis - physiology
Neoplasm Proteins - genetics
Neoplasm Proteins - metabolism
Organogenesis
Proteins
RNA Interference
Securin
Ubiquitin-Protein Ligase Complexes - genetics
Ubiquitin-Protein Ligase Complexes - metabolism
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Summary:The anaphase-promoting complex/cyclosome (APC/C) is a conserved ubiquitin ligase controlling mitosis and G1 phase of the cell cycle. The APC/C is activated by two regulatory subunits Cdc20 (APC/CCdc20) and Cdh1 (APC/CCdh1) to target securin, mitotic cyclins and other cell cycle regulatory proteins. Cdc20 is essential for sister chromatid separation at the meta- to anaphase transition in yeast, drosophila and perhaps mouse embryos. However, whether Cdc20 is essential for mitotic control of human somatic cells is uncertain. Therefore, we used a lentiviral vector-mediated inducible RNA interference (RNAi) system to generate strong downregulation of Cdc20 expression in clonal cells to further elucidate the role of human Cdc20. Here we show, that even an almost complete knockdown of Cdc20 below the detection limit in western blots does neither cause a mitotic block nor significant stabilization of the APCCdc20 substrates cyclin B and securin. Thus, there may be redundant mechanisms of mitotic control in the human somatic cell cycle.
ISSN:1538-4101
1551-4005
DOI:10.4161/cc.8.4.7810