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Science 7 June 1996:
Vol. 272. no. 5267, pp. 1470 - 1473
DOI: 10.1126/science.272.5267.1470
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Reports

Blockage by Adenovirus E4orf6 of Transcriptional Activation by the p53 Tumor Suppressor

Thomas Dobner, Nobuo Horikoshi, Susanne Rubenwolf, Thomas Shenk *

The adenovirus E4orf6 protein is shown here to interact with the cellular tumor suppressor protein p53 and to block p53-mediated transcriptional activation. The adenovirus protein inhibited the ability of p53 to bind to human TAFII31, a component of transcription factor IID (TFIID). Earlier work demonstrated that the interaction of p53 with TAFII31 involves a sequence near the NH2-terminus of p53, whereas the E4orf6-p53 interaction occurs within amino acids 318 to 360 of p53. Thus, the E4orf6 protein interacts at a site on p53 distinct from the domain that binds to TAFII31 but nevertheless inhibits the p53-TAFII31 interaction.

T. Dobner and S. Rubenwolf, Institut für Medizinische Mikrobiologie und Hygiene, Universität Regensburg, D-93042 Regensburg, Germany.
N. Horikoshi and T. Shenk, Howard Hughes Medical Institute, Department of Molecular Biology, Princeton University, Princeton, NJ 08544, USA.
* To whom correspondence should be addressed.


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Adenovirus E4orf6 oncoprotein modulates the function of the p53-related protein, p73.
F. Higashino, J. M. Pipas, and T. Shenk (1998)
PNAS 95, 15683-15687
   Abstract »    Full Text »    PDF »
p53 Status Does Not Determine Outcome of E1B 55-Kilodalton Mutant Adenovirus Lytic Infection.
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J. Virol. 72, 9479-9490
   Abstract »    Full Text »    PDF »
Inactivation of p53 but Not p73 by Adenovirus Type 5 E1B 55-Kilodalton and E4 34-Kilodalton Oncoproteins.
J. Roth, C. Konig, S. Wienzek, S. Weigel, S. Ristea, and M. Dobbelstein (1998)
J. Virol. 72, 8510-8516
   Abstract »    Full Text »    PDF »
RNA-Binding Activity of the E1B 55-Kilodalton Protein from Human Adenovirus Type 5.
J. J. Horridge and K. N. Leppard (1998)
J. Virol. 72, 9374-9379
   Abstract »    Full Text »    PDF »
The Early Region 4 orf4 Protein of Human Adenovirus Type 5 Induces p53-Independent Cell Death by Apoptosis.
R. C. Marcellus, J. N. Lavoie, D. Boivin, G. C. Shore, G. Ketner, and P. E. Branton (1998)
J. Virol. 72, 7144-7153
   Abstract »    Full Text »    PDF »
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Z. Li, A. D. Bailey, J. Buchowski, and A. M. Weiner (1998)
J. Virol. 72, 4205-4211
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Adenovirus Type 5 E4 Open Reading Frame 4 Protein Induces Apoptosis in Transformed Cells.
R. Shtrichman and T. Kleinberger (1998)
J. Virol. 72, 2975-2982
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J. Virol. 72, 2022-2032
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Inhibition of p53 Transactivation Function by the Human T-Cell Lymphotropic Virus Type 1 Tax Protein.
C. A. Pise-Masison, K.-S. Choi, M. Radonovich, J. Dittmer, S.-J. Kim, and J. N. Brady (1998)
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K. Qing, X.-S. Wang, D. M. Kube, S. Ponnazhagan, A. Bajpai, and A. Srivastava (1997)
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The adenovirus E4orf6 protein can promote E1A/E1B-induced focus formation by interfering with p53 tumor suppressor function.
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B. Datta, B. Li, D. Choubey, G. Nallur, and P. Lengyel (1996)
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An Adenovirus Mutant That Replicates Selectively in p53- Deficient Human Tumor Cells.
J. R. Bischoff, D. H. Kirn, A. Williams, C. Heise, S. Horn, M. Muna, L. Ng, J. A. Nye, A. Sampson-Johannes, A. Fattaey, et al. (1996)
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Genetic Analysis of a Potential Zinc-binding Domain of the Adenovirus E4 34k Protein.
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J. Biol. Chem. 275, 14969-14978
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Hepatitis C Virus Core Protein Enhances p53 Function through Augmentation of DNA Binding Affinity and Transcriptional Ability.
M. Otsuka, N. Kato, K.-H. Lan, H. Yoshida, J. Kato, T. Goto, Y. Shiratori, and M. Omata (2000)
J. Biol. Chem. 275, 34122-34130
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Human T-lymphotropic Virus Type I Tax Protein Utilizes Distinct Pathways for p53 Inhibition That Are Cell Type-dependent.
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