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Upregulation of BAK by butyrate in the colon is associated with increased Sp3 binding

Oncogene volume 25, pages 7192–7200 (2006)Cite this article

Abstract

Butyrate is a key bioactive product of dietary fibre fermentation thought to play a key role in cancer prevention. One contributory mechanism in this role is the regulation of apoptosis by butyrate. As butyrate shows low levels of toxicity, the mechanisms by which it triggers or regulates apoptosis are of great interest. We and others have shown that the proapoptotic protein BAK is upregulated by butyrate. We show here that this observation is conserved across multiple cell lines, that it occurs in all cells in a population and is at the transcriptional level. We have used a promoter-reporter construct to identify the regulatory regions of the BAK promoter and found that much of the transcriptional activity occurs via a single Sp1/Sp3 binding site. We have shown that both Sp1 and Sp3 bind, but upon butyrate treatment Sp1 binding decreases in favour of Sp3 binding. We speculate that this may be an acetylation-mediated event.

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Acknowledgements

We thank Professor C Dive for her support and encouragement throughout this study, Professor B Vogelstein for HCT116 Bax−/−, Mr DWC Chen for technical support and Dr E Williams for a critical reading of the manuscript. This work was funded by BBSRC Grants 34/D16937 and 50/D19346.

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Authors and Affiliations

  1. Division of Clinical Sciences North, Human Nutrition Unit, University of Sheffield, Northern General Hospital, Sheffield, UK

    H Chirakkal, S H Leech, J S Waby & B M Corfe

  2. School of Biological Sciences, University of Manchester, Manchester, UK

    K E Brookes & A L Prais

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  1. H Chirakkal
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  2. S H Leech
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  3. K E Brookes
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  4. A L Prais
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  5. J S Waby
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  6. B M Corfe
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Correspondence to B M Corfe.

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Chirakkal, H., Leech, S., Brookes, K. et al. Upregulation of BAK by butyrate in the colon is associated with increased Sp3 binding. Oncogene 25, 7192–7200 (2006). https://doi.org/10.1038/sj.onc.1209702

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