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Molecular and Cellular Biology, April 1999, p. 2635-2643, Vol. 19, No. 4
0270-7306/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

Synergism with Germ Line Transcription Factor Oct-4: Viral Oncoproteins Share the Ability To Mimic a Stem Cell-Specific Activity

A. Brehm,1,dagger K. Ohbo,1 W. Zwerschke,2 V. Botquin,1 P. Jansen-Dürr,2,Dagger and H. R. Schöler1,*

Gene Expression Programme, European Molecular Biology Laboratory, 69117 Heidelberg,1 and Deutsches Krebsforschungszentrum, Angewandte Tumorvirologie, 69120 Heidelberg,2 Federal Republic of Germany

Received 6 November 1998/Returned for modification 9 December 1998/Accepted 18 January 1999

Activation of transcription by Oct-4 from remote binding sites requires a cofactor that is restricted to embryonal stem cells. The adenovirus E1A protein can mimic the activity of this stem cell-specific factor and stimulates Oct-4 activity in differentiated cells. Here we characterize the Oct-4-E1A interaction and show that the E1A 289R protein harbors two independent Oct-4 binding sites, both of which specifically interact with the POU domain of Oct-4. Furthermore, we demonstrate that, like E1A, the human papillomavirus E7 oncoprotein also specifically binds to the Oct-4 POU domain. E7 and Oct-4 can form a complex both in vitro and in vivo. Expression of E7 in differentiated cells stimulates Oct-4-mediated transactivation from distal binding sites. Moreover, Oct-4, but not other Oct factors, is active when expressed in cells transformed by human papillomavirus. Our results suggest that different viruses have evolved oncoproteins that share the ability to target Oct-4 and to mimic a stem cell-specific activity.

* Corresponding author. Mailing address: Gene Expression Programme, European Molecular Biology Laboratory, Meyerhofstrasse 1, 69117 Heidelberg, Federal Republic of Germany. Phone: 6221-387-550. Fax: 6221-387-518. E-mail: Schoeler{at}EMBL-Heidelberg.DE.

dagger Present address: Wellcome/CRC Institute, Cambridge CB2 1QR, United Kingdom.

Dagger Present address: Institut für Biomedizinische Alternsforschung, 6020 Innsbruck, Austria.

Molecular and Cellular Biology, April 1999, p. 2635-2643, Vol. 19, No. 4
0270-7306/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.


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