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p53 promotes adenoviral replication and increases late viral gene expression

Oncogene volume 25, pages 1509–1520 (2006)Cite this article

Abstract

The tumor suppressor protein, p53, plays a critical role in viro-oncology. However, the role of p53 in adenoviral replication is still poorly understood. In this paper, we have explored further the effect of p53 on adenoviral replicative lysis. Using well-characterized cells expressing a functional p53 (A549, K1neo, RKO) and isogenic derivatives that do not (K1scx, RKOp53.13), we show that virus replication, late virus protein expression and both wtAd5 and ONYX-015 virus-induced cell death are impaired in cells deficient in functional p53. Conversely, by transfecting p53 into these and other cells (IIICF/c, HeLa), we increase late virus protein expression and virus yield. We also show, using reporter assays in IIICF/c, HeLa and K1scx cells, that p53 can cooperate with E1a to enhance transcription from the major late promoter of the virus. Late viral protein production is enhanced by exogenous p53. Taken together, our data suggest that functional p53 can promote the adenovirus (Ad) lytic cycle. These results have implications for the use of Ad mutants that are defective in p53 degradation, such as ONYX-015, as agents for the treatment of cancers.

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Acknowledgements

We thank Mike Kastan (Johns Hopkins, Baltimore) for the RKO pair of cells, Roger Reddel (CMRI, Sydney) for the IIICF/c p53 null human fibroblast cell line, Walter Doerfler (Institut fur Genetik, Cologne) for the MLPCAT plasmid, and Peter van der Vliet (University Medical Center, Utrecht) for the DBP antibody. We wish to thank Nicky Real, Deidre Dobson-Le, Craig Homer and Rhodri Harfoot for technical assistance. This work was supported by grants from the Royal Society and the Health Research Council of New Zealand.

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  1. B R Dix

    Present address: School of Pharmacy, Curtin University, Perth, Australia

Authors and Affiliations

  1. Department of Pathology, University of Otago, Dunedin, New Zealand

    J A Royds, B R Dix, L Hananeia, I A Russell, A Wiles & A W Braithwaite

  2. Department of Microbiology, University of Otago, Dunedin, New Zealand

    M Hibma

  3. Department of Pathology, University of Wales College of Medicine, Cardiff, Wales, UK

    D Wynford-Thomas

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Correspondence to J A Royds.

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Royds, J., Hibma, M., Dix, B. et al. p53 promotes adenoviral replication and increases late viral gene expression. Oncogene 25, 1509–1520 (2006). https://doi.org/10.1038/sj.onc.1209185

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