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Silencing of human Int-6 impairs mitosis progression and inhibits cyclin B–Cdk1 activation

Oncogene volume 24, pages 1203–1211 (2005)Cite this article

Abstract

The Int-6 protein has been originally identified as the product of a mouse gene being a frequent integration site of the mouse mammary tumour virus. Here, we show that reducing Int-6 expression by RNA interference in HeLa cells markedly alters mitosis progression. Defects in spindle formation, chromosome segregation and cytokinesis were observed. These abnormalities of mitosis completion are correlated with an inhibition of cyclin B–Cdk1 kinase activity, due to a prolonged inhibitory phosphorylated state of Cdk1. In line with this observation, the Wee1 tyrosine kinase that negatively controls Cdk1 was less efficiently inactivated during G2 in Int-6-depleted cells. These findings support the notion that the oncogenic properties associated with alteration of Int-6 originate from chromosomal instability.

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Acknowledgements

We wish to thank A Roisin for technical help. We are also grateful to F Magdinier, E Gilson, V Mouly and G Butler-Browne for providing us with the cell line of human fibroblats expressing hTERT. This work was supported by the Ligue Nationale contre le cancer (‘équipes labellisées' programme) and by the Région Rhône-Alpes (INA cancer programme).

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  1. Laboratoire de Biologie Moléculaire de la Cellule, UMR5161 – CNRS, IFR 128 Biosciences Lyon-Gerland, ENS de Lyon, 46, Allée d'Italie, 69364, Lyon, France

    Christelle Morris & Pierre Jalinot

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  2. Pierre Jalinot
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Correspondence to Pierre Jalinot.

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Supplementary Information accompanies the paper on Oncogene website (http://www.nature.com/onc)

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Morris, C., Jalinot, P. Silencing of human Int-6 impairs mitosis progression and inhibits cyclin B–Cdk1 activation. Oncogene 24, 1203–1211 (2005). https://doi.org/10.1038/sj.onc.1208268

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