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J Biol Chem, Vol. 275, Issue 1, 87-94, January 7, 2000
From the Department of Biochemistry, School of Medical Sciences,
University of Bristol, Bristol BS8 1TD, United Kingdom and the
The human papillomavirus (HPV) E2 protein
regulates viral gene expression and is also required for viral
replication. HPV-transformed cells often contain chromosomally
integrated copies of the HPV genome in which the viral E2 gene is
disrupted. We have shown previously that re-expression of the HPV 16 E2
protein in HPV 16-transformed cells results in cell death via
apoptosis. Here we show that the HPV 16 E2 protein can induce apoptosis
in both HPV-transformed and non-HPV-transformed cell lines. E2-induced apoptosis is abrogated by a trans-dominant negative mutant of p53 or by
overexpression of the HPV 16 E6 protein, but is increased by
overexpression of wild-type p53. We show that mutations that block the
DNA binding activity of E2 do not impair the ability of this protein to
induce apoptosis. In contrast, removal of both N-terminal domains from
the E2 dimer completely blocks E2-induced cell death. Heterodimers
formed between wild-type E2 and N-terminally deleted E2 proteins also
fail to induce cell death. Our data suggest that neither the DNA
binding activity of E2 nor other HPV proteins are required for the
induction of apoptosis by E2 and that E2-induced cell death occurs via
a p53-dependent pathway.
The Human Papillomavirus (HPV) 16 E2 Protein Induces
Apoptosis in the Absence of Other HPV Proteins and via a
p53-dependent Pathway*
,
, Paterson Institute for Cancer Research, Christie Hospital NHS
Trust, Manchester M20 9BX, United Kingdom
*
The costs of publication of this
article were defrayed in part by the
payment of page charges. The article
must therefore be hereby marked
"advertisement" in
accordance with 18 U.S.C. Section
1734 solely to indicate this fact.
Recipient of a United Kingdom Biotechnology and Biological
Sciences Research Council Ph.D. studentship.
§
Recipient of a United Kingdom Biotechnology and Biological Sciences
Research Council and Generic Biologicals Ltd. Cooperative Awards in
Science and Engineering Ph.D. studentship.
¶
Present address: School of Biological Sciences, University of
Sussex, Falmer BN1 9QG, United Kingdom.
**
To whom correspondence should be addressed. Tel.: 0117-954-6852;
Fax: 0117-928-8274; E-mail: Kevin.Gaston@Bristol.ac.uk.
Copyright © 2000 by The American Society for Biochemistry and Molecular Biology, Inc.
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