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Molecular and Cellular Biology, January 1999, p. 846-854, Vol. 19, No. 1
Department of Molecular Genetics and
Biochemistry, University of Pittsburgh School of Medicine,
Pittsburgh, Pennsylvania 15261
Received 21 April 1998/Returned for modification 26 May
1998/Accepted 6 October 1998
The retinoblastoma tumor suppressor protein, Rb, interacts directly
with the largest TATA-binding protein-associated factor, TAFII250, through multiple regions in each protein. To
define the potential role(s) of this interaction, we examined whether Rb could regulate the intrinsic, bipartite kinase activity of TAFII250. Here, we report that Rb is able to inhibit the
kinase activity of immunopurified and gel-purified recombinant
TAFII250. Rb inhibits the autophosphorylation of
TAFII250 as well as its phosphorylation of the RAP74
subunit of TFIIF in a dose-responsive manner. Inhibition of
TAFII250 kinase activity involves the Rb pocket (amino
acids 379 to 928) but not its amino terminus. In addition, Rb appears
to specifically inhibit the amino-terminal kinase domain of
TAFII250 through a direct protein-protein interaction. We
further demonstrate that two different tumor-derived Rb pocket mutants,
C706F and
0270-7306/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.
Rb Inhibits the Intrinsic Kinase Activity of
TATA-Binding Protein-Associated Factor TAFII250
ex22, are functionally defective for kinase inhibition,
even though they are able to bind the amino terminus of
TAFII250. Our results suggest a novel mechanism of
transcriptional regulation by Rb, involving direct interaction with
TAFII250 and inhibition of its ability to phosphorylate
itself, RAP74, and possibly other targets.
*
Corresponding author. Mailing address: Department of
Molecular Genetics and Biochemistry, W1246 Biomedical Science Tower, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261. Phone: (412) 648-9268. Fax: (412) 383-8837. E-mail:
probb{at}pop.pitt.edu.
Molecular and Cellular Biology, January 1999, p. 846-854, Vol. 19, No. 1
0270-7306/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.
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