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Vol. 12, No. 11, pp. 1621-1637, June 1, 1998
Department of Biochemistry and
1 Howard Hughes Medical
Institute, University of Medicine and Dentistry of New Jersey, Robert
Wood Johnson Medical School, Piscataway, New Jersey 08854 USA
RBP is a cellular protein that functions as a transcriptional
repressor in mammalian cells. RBP has elicited great interest lately
because of its established roles in regulating gene expression, in
Drosophila and mouse development, and as a component of the Notch signal transduction pathway. This report focuses on the mechanism
by which RBP represses transcription and thereby regulates expression
of a relatively simple, but natural, promoter. The results show that,
irrespective of the close proximity between RBP and other transcription
factors bound to the promoter, RBP does not occlude binding by these
other transcription factors. Instead, RBP interacts with two
transcriptional coactivators: dTAFII110, a subunit of TFIID,
and TFIIA to repress transcription. The domain of dTAFII110
targeted by RBP is the same domain that interacts with TFIIA, but is
disparate from the domain that interacts with Sp1. Repression can be
thwarted when stable transcription preinitiation complexes are formed
before RBP addition, suggesting that RBP interaction with TFIIA and
TFIID perturbs optimal interactions between these coactivators.
Consistent with this, interaction between RBP and TFIIA precludes
interaction with dTAFII110. This is the first report of a
repressor specifically targeting these two coactivators to subvert
activated transcription.
[Key Words: RBP; transcriptional repression; TFIIA/TFIID targeting]
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