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Mol Cell Biol, May 1998, p. 2997-3009, Vol. 18, No. 5
Department of Microbiology and the Institute
for Cellular and Molecular Biology, University of Texas at Austin,
Texas 78712-1095,1 and
Institute of
Molecular Genetics, Czech Academy of Sciences, 166 37 Prague 6, Czech Republic2
Received 23 June 1997/Returned for modification 11 August
1997/Accepted 29 January 1998
v-rel is the oncogenic member of the Rel/NF-
0270-7306/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.
AP-1 Factors Play an Important Role in
Transformation Induced by the v-rel Oncogene
B family
of transcription factors. The mechanism by which v-Rel induces
transformation of avian lymphoid cells and fibroblasts is not precisely
known. However, most models propose that v-rel disrupts the
normal transcriptional regulatory network. In this study we evaluated
the role of AP-1 family members in v-Rel-mediated transformation. The
overexpression of v-Rel, c-Rel, and c-Rel
resulted in a prolonged
elevation of c-fos and c-jun expression and in
a sustained repression of fra-2 at both the mRNA and
protein levels in fibroblasts and lymphoid cells. Moreover, the
transforming abilities of these Rel proteins correlated with their
ability to alter the expression of these AP-1 factors. v-Rel exhibited
the most pronounced effect, whereas c-Rel, with poor transforming
ability, elicited only moderate changes in AP-1 levels. Furthermore,
c-Rel
, which exhibits enhanced transforming potential relative to
c-Rel, induced intermediate changes in AP-1 expression. To directly
evaluate the role of AP-1 family members in the v-Rel transformation
process, a supjun-1 transdominant mutant was used. The
supjun-1 mutant functions as a general inhibitor of AP-1
activity by inhibiting AP-1-mediated transactivation and by reducing
AP-1 DNA-binding activity. Coinfection or sequential infection of
fibroblasts or lymphoid cells with viruses carrying rel
oncogenes and supjun-1 resulted in a reduction of the
transformation efficiency of the Rel proteins. The expression of
supjun-1 inhibited the ability of v-Rel transformed
lymphoid cells and fibroblasts to form colonies in soft agar by over
70%. Furthermore, the expression of supjun-1 strongly
interfered with the ability of v-Rel to morphologically transform avian
fibroblasts. This is the first report showing that v-Rel might execute
its oncogenic potential through modulating the activity of early
response genes.
*
Corresponding author. Mailing address: Department of
Microbiology, University of Texas at Austin, Austin, TX 78712-1095. Phone: (512) 471-5525. Fax: (512) 471-7088. E-mail:
bose{at}mail.utexas.edu.
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