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J. Biol. Chem., Vol. 277, Issue 25, 22297-22303, June 21, 2002
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§,
¶,
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**,
, and

From the The human papillomavirus (HPV)
transcription/replication factor E2 is essential for the life cycle of
HPVs. E2 protein binds to DNA target sequences in the viral long
control regions to regulate transcription of the viral genome.
It also enhances viral DNA replication by interacting with the viral
replication factor E1 and recruiting it to the origin of replication
and may also play a more direct role in replication. The cellular
proteins with which E2 interacts to carry out these functions are
largely unknown. To identify these proteins a yeast two-hybrid screen
was carried out with the transcription/replication domain of HPV16 E2.
This screen identified several candidate interacting partners for E2 including TopBP1 (topoisomerase II
Institute of Comparative Medicine,
Department of Veterinary Pathology, University of Glasgow, Garscube
Estate, Bearsden Road, Glasgow G61 1QH, Scotland, the
§ Beatson Institute for Cancer Research, Garscube Estate,
Glasgow G61 1BD, Scotland, and the
Laboratory of Biomedical
Research, Institute of Molecular and Cellular Biosciences, University
of Tokyo, 1-1-1, Yayoi, Bunkyo-ku, Tokyo 113 0032, Japan
-binding protein 1). TopBP1 has
eight BRCA1 carboxyl-terminal domains that are found in proteins regulating the DNA damage response, transcription, and replication. Here we demonstrate that HPV16 E2 and TopBP1 interact in
vitro and in vivo and that TopBP1 can enhance the
ability of E2 to activate transcription and replication. This is the
first time that TopBP1 has been shown to function as a transcriptional
coactivator and that E2 interacts with TopBP1. Removal of the
amino-terminal domain of TopBP1 abolishes coactivation of transcription
and replication. This interaction may have functional consequences upon
the viral life cycle.

To whom correspondence should be addressed. Tel.:
44-141-330-3155; Fax: 44-141-330-5602; E-mail:
i.morgan@vet.gla.ac.uk.
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