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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. Access through your institution Buy or subscribe This is a preview of subscription content, access via your institution ACCESS OPTIONS

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institutional subscriptions * Read our FAQs * Contact customer support SIMILAR CONTENT BEING VIEWED BY OTHERS IXOVEX-1, A NOVEL ONCOLYTIC E1B-MUTATED ADENOVIRUS Article Open access 20 May

2022 ENHANCED ONCOLYTIC ADENOVIRAL PRODUCTION BY DOWNREGULATION OF DEATH-DOMAIN ASSOCIATED PROTEIN AND OVEREXPRESSION OF PRECURSOR TERMINAL PROTEIN Article Open access 13 January 2021 HUMAN

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Edwards SJ, Hananeia L, Lasham A, Royds J _et al_. (2003). _Oncogene_ 22: 2782–2794. Download references 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. AUTHOR INFORMATION Author notes * B R Dix Present address: School of Pharmacy, Curtin University, Perth,

Australia AUTHORS AND AFFILIATIONS * 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 *

Department of Microbiology, University of Otago, Dunedin, New Zealand M Hibma * Department of Pathology, University of Wales College of Medicine, Cardiff, Wales, UK D Wynford-Thomas Authors

* J A Royds View author publications You can also search for this author inPubMed Google Scholar * M Hibma View author publications You can also search for this author inPubMed Google

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inPubMed Google Scholar * D Wynford-Thomas View author publications You can also search for this author inPubMed Google Scholar * A W Braithwaite View author publications You can also search

for this author inPubMed Google Scholar CORRESPONDING AUTHOR Correspondence to J A Royds. RIGHTS AND PERMISSIONS Reprints and permissions ABOUT THIS ARTICLE CITE THIS ARTICLE 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 Download

citation * Received: 17 February 2004 * Revised: 17 August 2005 * Accepted: 18 August 2005 * Published: 24 October 2005 * Issue Date: 09 March 2006 * DOI:

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currently available for this article. Copy to clipboard Provided by the Springer Nature SharedIt content-sharing initiative KEYWORDS * p53 * adenovirus * E1b55kDa * oncology