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Journal of Virology, November 2002, p. 11042-11053, Vol. 76, No. 21
0022-538X/02/$04.00+0     DOI: 10.1128/JVI.76.21.11042-11053.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Cooperative Activation of Human Papillomavirus Type 8 Gene Expression by the E2 Protein and the Cellular Coactivator p300

Andreas Müller,1 Andreas Ritzkowsky,2 and Gertrud Steger1*

Institute of Virology, University of Cologne, 50935 Cologne,1 Institute of Dermatology, University of Cologne, 50931 Cologne, Germany2

Received 29 April 2002/ Accepted 24 July 2002

The E2 proteins of papillomaviruses (PV) bind to the coactivator CBP/p300 as do many other transcription factors, but the precise role of CBP/p300 in E2-specific functions is not yet understood. We show that the E2 protein of human PV type 8 (HPV8) directly binds to p300. Activation of HPV8 gene expression by low amounts of HPV8 E2 was stimulated up to sevenfold by coexpression of p300. The interaction between E2 and p300 may play a role in differentiation-dependent activation of PV gene expression, since we can show that the expression level of p300 increases during keratinocyte differentiation. Surprisingly, sequence-specific binding of E2 to its recognition sites within the regulatory region of HPV8 is not necessary for this cooperation, indicating that E2 can be recruited to the promoter via protein-protein interaction. HPV8 E2 binds via its N-terminal activation domain (AD), its C-terminal DNA binding domain (DBD), and its internal hinge region to p300 in vitro. Transient-transfection assays revealed that the AD is necessary and sufficient for cooperative activation with p300. However, we provide evidence that the interaction of the hinge and the DBD of HPV8 E2 with p300 may contribute. Our data suggest an important role of p300 in regulation of HPV8 gene expression and reveal a new mechanism by which E2 may be recruited to a promoter to activate transcription without sequence specific DNA binding.

* Corresponding author. Mailing address: Institute of Virology, University of Cologne, Fürst-Pückler-Strasse 56, 50935 Cologne, Germany. Phone: 49-221-478-3926. Fax: 49-221-478-3902. E-mail: Gertrud.Steger{at}uni-koeln.de.

Journal of Virology, November 2002, p. 11042-11053, Vol. 76, No. 21
0022-538X/02/$04.00+0     DOI: 10.1128/JVI.76.21.11042-11053.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



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