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A Lin-9 complex is recruited by B-Myb to activate transcription of G2/M genes in undifferentiated embryonal carcinoma cells

Oncogene volume 28, pages 1737–1747 (2009)Cite this article

Abstract

It has recently been discovered that cell-cycle gene transcription is regulated by a core complex named LINC that switches from a transcriptionally repressive complex in G0–G1 with the p130 or p107 pocket proteins and E2F4 to a transcriptionally active complex in S–G2 containing B-Myb. We have studied the function of LINC in F9 embryonal carcinoma cells, which are distinguished by a rapid cell cycle resulting from an extremely short G1 phase. We show that suppressing expression of the LINC component, Lin-9, in F9 cells causes arrest in mitosis, and we have used this system to screen for transcriptional targets. In these cells, B-Myb was found in complexes with Lin-9 and several other LINC constituents, however, the pocket proteins did not associate with LINC unless F9 cells were differentiated. Lin-9 and B-Myb were both required for transcription of G2/M genes such as Cyclin B1 and Survivin. Moreover, B-Myb was demonstrated to recruit Lin-9 to the Survivin promoter through multiple Myb-binding sites. The demonstration that a B-Myb/LINC complex is vital for progression through mitosis in cells lacking a G1/S checkpoint has implications for both undifferentiated embryonal cells and for cancers in which pocket protein function is compromised.

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Acknowledgements

We thank Stephan Gaubatz and Alexander Brehm for the kind gifts of LINC antibodies and human Lin-9 cDNA, respectively. This work was supported by a project grant from the Association for International Cancer Research (06-030).

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  1. M Notaridou

    Present address: 2Current address: Department of Gynaecological Oncology, Elizabeth Garrett Anderson Institute of Women's Health, University College London, London, UK.,

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  1. Department of Virology, Faculty of Medicine, Imperial College London, London, UK

    A S Knight, M Notaridou & R J Watson

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  1. A S Knight
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Correspondence to R J Watson.

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

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Knight, A., Notaridou, M. & Watson, R. A Lin-9 complex is recruited by B-Myb to activate transcription of G2/M genes in undifferentiated embryonal carcinoma cells. Oncogene 28, 1737–1747 (2009). https://doi.org/10.1038/onc.2009.22

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