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Journal of Virology, November 2003, p. 11809-11821, Vol. 77, No. 21
0022-538X/03/$08.00+0     DOI: 10.1128/JVI.77.21.11809-11821.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

Adenovirus E1B 55-Kilodalton Oncoprotein Binds to Daxx and Eliminates Enhancement of p53-Dependent Transcription by Daxx

Lisa Y. Zhao,1 April L. Colosimo,2,{dagger} Yue Liu,2,{ddagger} Yanping Wan,2 and Daiqing Liao1*

Department of Anatomy and Cell Biology and Shands Cancer Center, University of Florida College of Medicine, Gainesville, Florida 32610-0235,1 Department of Microbiology and Infectious Diseases, Faculty of Medicine, Université de Sherbrooke, Sherbrooke, Quebec J1H 5N4, Canada2

Received 23 May 2003/ Accepted 1 August 2003

The adenovirus E1B 55-kDa protein impairs the p53 pathway and enhances transformation, although the underlying mechanisms remain to be defined. We found that Daxx binds to the E1B 55-kDa protein in a yeast two-hybrid screen. The two proteins interact through their C termini. Mutation of three potential phosphorylation sites (S489/490 and T494 to alanine) within the E1B 55-kDa protein did not affect its interaction with Daxx, although such mutations were previously shown to inhibit E1B's ability to repress p53-dependent transcription and to enhance transformation. In addition to their coimmunoprecipitation in 293 extracts, purified Daxx interacted with the E1B 55-kDa protein in vitro, indicating their direct interaction. In 293 cells, Daxx colocalized with the E1B 55-kDa protein within discrete nuclear dots, where p53 was also found. Such structures were distinct from PML (promyelocytic leukemia protein) bodies, and it appeared that Daxx was displaced from PML bodies. Thus, the Daxx concentration was diminished in dots with a prominent presence of PML and vice versa. Indeed, PML overexpression led to dramatic redistribution of Daxx from p53-E1B 55-kDa protein complexes to PML bodies. Additionally, expression of the E1B 55-kDa protein in Saos2 osteosarcoma cells reduced the number of PML bodies. Our data suggest that E1B and PML compete for available Daxx in the cell. Surprisingly, Daxx significantly augmented p53-mediated transcription and the E1B 55-kDa protein eliminated this effect. Thus, it is likely that the E1B 55-kDa protein sequesters Daxx and p53 in specific nuclear locations, where p53 cannot activate transcription. One consequence of the Daxx-E1B interaction might be an alteration of normal interactions of Daxx, PML, and p53, which may contribute to cell transformation.

* Corresponding author. Mailing address: Department of Anatomy and Cell Biology, University of Florida College of Medicine, P.O. Box 100235, 1600 SW Archer Rd., Gainesville, FL 32610-0235. Phone: (352) 294-7976. Fax: (352) 392-3305. E-mail: dliao{at}ufl.edu.

{dagger} Present address: Lady Davis Institute, McGill University, Montreal, Quebec H3T 1E2, Canada.

{ddagger} Molecular Biology Institute, University of California, Los Angeles, Los Angeles, CA 90095.

Journal of Virology, November 2003, p. 11809-11821, Vol. 77, No. 21
0022-538X/03/$08.00+0     DOI: 10.1128/JVI.77.21.11809-11821.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.



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