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J Gen Virol 78 (1997), 413-421
© 1997 Society for General Microbiology

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Journal of General Virology, Vol 78, 413-421, Copyright © 1997 by Society for General Microbiology


ARTICLES

The E1A N terminus (aa 1-29) of the highly oncogenic adenovirus type 12 harbours a trans-activation function not detectable in the non- oncogenic serotype 2

KS Lipinski, G Kroner-Lux, H Esche and D Brockmann
Institute of Molecular Biology (Cancer Research), University of Essen Medical School, FRG.

Early region 1A (E1A) of adenoviruses (Ad) codes for potent activator and repressor molecules which are involved in the regulation of viral and cellular gene expression. Gene regulatory functions of E1A proteins are mainly located in their conserved regions (CR) 1 to 3. In addition to the CRs, specific amino acids (aa) of the N-terminal end play an important role in some gene regulatory functions. We describe here the identification and characterization of a novel trans-activation domain which is located in the non-conserved N-terminal end of Ad12 E1A, namely aa 1-29. Fusion of this region to the DNA-binding domain of the yeast transcription factor Gal4 generates a strong trans-activator which induces gene expression of reporter constructs in dependence on Gal4 DNA-binding sites. Furthermore, transient expression assays using the physiological E1A-responsive adenoviral E2 early promoter revealed that the N terminus is involved in its activation. The gene regulatory function of the N terminus is specific for E1A proteins of the highly oncogenic serotype Ad12, as the respective E1A N terminus of the non- oncogenic serotype Ad2 is unable to activate the expression of the reporter gene as Gal4 fusion protein. Moreover, deletion mutant analyses demonstrate that Ad12 E1A proteins carry three independently acting activation domains: (1) aa 1-29, (2) CR1 and (3) CR3.


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N. Avvakumov, R. Wheeler, J. C. D'Halluin, and J. S. Mymryk
Comparative Sequence Analysis of the Largest E1A Proteins of Human and Simian Adenoviruses
J. Virol., July 17, 2002; 76(16): 7968 - 7975.
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P. Fax, K. S. Lipinski, H. Esche, and D. Brockmann
cAMP-independent Activation of the Adenovirus Type 12 E2 Promoter Correlates with the Recruitment of CREB-1/ATF-1, E1A12S, and CBP to the E2-CRE
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J. Biol. Chem.Home page
P. Fax, O. Lehmkuhler, C. Kuhn, H. Esche, and D. Brockmann
E1A12S-mediated Activation of the Adenovirus Type 12 E2 Promoter Depends on the Histone Acetyltransferase Activity of p300/CBP
J. Biol. Chem., December 15, 2000; 275(51): 40554 - 40560.
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Copyright © 1997 by the Society for General Microbiology.