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Regulation of mitotic exit by the RNF8 ubiquitin ligase

Oncogene volume 27, pages 1355–1365 (2008)Cite this article

Abstract

RNF8 is a ubiquitin ligase with a FHA domain near its N terminus, and a RING-finger domain at its C terminus, through which it recruits several ubiquitin-conjugating enzymes. In metazoans, only the mitotic checkpoint regulator CHFR shares this domain architecture. Here we show that RNF8 is a nuclear protein that follows a cell-cycle-dependent turnover, reaching its highest levels in mitosis, followed by a strong decline in late mitotic stages. Overexpression of RNF8 caused a delay in cytokinesis and the frequent appearance of aberrant mitotic figures. These effects were dependent on the ubiquitin ligase activity of RNF8, since they were significantly attenuated when a RING-finger mutant, inactive as an E3, was overexpressed. Depletion of RNF8 also caused a delay in the exit from the mitotic arrest induced by nocodazole, associated with a reduced turnover of the APC/C substrate cyclin B1. These observations suggest that RNF8 regulates the rate of exit from mitosis and cytokinesis.

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Acknowledgements

We thank J Comas for technical assistance with flow cytometry. This work was supported by Ministry of Science grants SAF2001-1969 and SAF2005-05109-CO2-01 (to TMT). VP was funded by a CIRIT predoctoral fellowship.

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  1. V Plans

    Present address: 2Current address: FMP/MDC, Leibniz-Institut für Molekulare Pharmakologie and Max-Delbrück-Zentrum für Molekulare Medizin, Robert-Rossle Strasse 10, Berlin D-13125, Germany.,

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  1. Department of Molecular and Cellular Biology, Instituto de Biología Molecular de Barcelona, Consejo Superior de Investigaciones Científicas, Barcelona, Spain

    V Plans, M Guerra-Rebollo & T M Thomson

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  1. V Plans
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Correspondence to T M Thomson.

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Plans, V., Guerra-Rebollo, M. & Thomson, T. Regulation of mitotic exit by the RNF8 ubiquitin ligase. Oncogene 27, 1355–1365 (2008). https://doi.org/10.1038/sj.onc.1210782

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