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Molecular and Cellular Biology, September 1999, p. 6458-6468, Vol. 19, No. 9
Department of Anatomy, University of
Wisconsin Medical School, Madison, Wisconsin
53706,1 and Laboratory of Molecular
Oncology, Massachusetts General Hospital Cancer Center,
Charlestown, Massachusetts 021292
Received 2 April 1999/Returned for modification 18 May
1999/Accepted 8 June 1999
Complexes between the retinoblastoma protein (pRb) and the
transcription factor E2F-1 are thought to be important for regulating cell proliferation. We have shown previously that the E7 oncoprotein from human papillomavirus type 16, dependent upon its binding to pRb
proteins, induces proliferation, disrupts differentiation, and induces
apoptosis when expressed in the differentiating, or fiber, cells of the
ocular lenses in transgenic mice. Mice that carry a null mutation in
E2F-1 do not exhibit any defects in proliferation and
differentiation in the lens. By examining the lens phenotype in mice
that express E7 on an E2F-1 null background, we now show genetic evidence that E7's ability to alter the fate of fiber cells is
partially dependent on E2F-1. On the other hand,
E2F-1 status does not affect E7-induced proliferation in
the undifferentiated lens epithelium. These data provide genetic
evidence that E2F-1, while dispensible for normal fiber
cell differentiation, is one mediator of E7's activity in vivo and
that the requirement for E2F-1 is context dependent. These
data suggest that an important role for pRb-E2F-1 complex during fiber
cell differentiation is to negatively regulate cell cycle progression,
thereby allowing completion of the differentiation program to occur.
0270-7306/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.
Disruption of Retinoblastoma Protein Family Function by Human
Papillomavirus Type 16 E7 Oncoprotein Inhibits Lens Development in
Part through E2F-1

*
Corresponding author. Mailing address: Department of
Anatomy, University of Wisconsin Medical School, 1300 University Ave., Madison, WI 53706. Phone: 608-262-8988. Fax: 608-262-7306. E-mail: aegriep{at}facstaff.wisc.edu.
Present address: Department of Biological Sciences, Columbia
University, 1212 Amsterdam Ave., New York, NY 10027.
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