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Molecular and Cellular Biology, March 2000, p. 1616-1625, Vol. 20, No. 5
0270-7306/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.
Cubitus interruptus Requires Drosophila
CREB-Binding Protein To Activate wingless Expression in the
Drosophila Embryo
Yang
Chen,1,
R. H.
Goodman,1 and
Sarah M.
Smolik2,*
Vollum Institute1 and
Department of Cell and Developmental
Biology,2 Oregon Health Sciences University,
Portland, Oregon 97201
Received 29 July 1999/Returned for modification 23 September
1999/Accepted 23 November 1999
CREB-binding protein (CBP) serves as a transcriptional coactivator
in multiple signal transduction pathways. The Drosophila homologue of CBP, dCBP, interacts with the transcription factors Cubitus interruptus (CI), MAD, and Dorsal (DL) and functions as a
coactivator in several signaling pathways during Drosophila development, including the hedgehog (hh),
decapentaplegic (dpp), and Toll
pathways. Although dCBP is required for the expression of the
hh target genes, wingless (wg) and
patched (ptc) in vivo, and potentiates
ci-mediated transcriptional activation in vitro, it is not
known that ci absolutely requires dCBP for its activity. We
used a yeast genetic screen to identify several ci point
mutations that disrupt CI-dCBP interactions. These mutant proteins are
unable to transactivate a reporter gene regulated by ci
binding sites and have a lower dCBP-stimulated activity than wild-type
CI. When expressed exogenously in embryos, the CI point mutants cannot activate endogenous wg expression. Furthermore, a CI mutant
protein that lacks the entire dCBP interaction domain functions as a
negative competitor for wild-type CI activity, and the expression of
dCBP antisense RNAs can suppress CI transactivation in Kc cells. Taken together, our data suggest that dCBP function is necessary for ci-mediated transactivation of wg during
Drosophila embryogenesis.
*
Corresponding author. Mailing address: Department of
Cell and Developmental Biology, L-215, Oregon Health Sciences
University, 3181 SW Sam Jackson Park Rd., Portland, OR 97201. Phone:
(503) 494-7192. Fax: (503) 494-4353. E-mail: smoliks{at}ohsu.edu.

Present address: Myriad Genetics, Inc., Salt Lake City, UT
84108.
Molecular and Cellular Biology, March 2000, p. 1616-1625, Vol. 20, No. 5
0270-7306/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.
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