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Mol. Cell. Biol., Jan 1995, 227-234, Vol 15, No. 1
N Horikoshi, A Usheva, J Chen, AJ Levine, R Weinmann and T Shenk
The tumor suppressor gene product p53 can activate and repress
transcription. Both transcriptional activation and repression are thought
to involve the direct interaction of p53 with the basal transcriptional
machinery. Previous work has demonstrated an in vitro interaction between
p53 and the TATA-binding protein that requires amino acids 20 to 57 of p53
and amino acids 220 to 271 of the TATA- binding protein. The present
results show that a 75-amino-acid segment from the carboxy terminus of p53
also can bind to the TATA-binding protein in vitro, and this interaction
requires amino acids 217 to 268 of the TATA-binding protein, essentially
the same domain that is required for interaction with the amino-terminal
domain of p53. A carboxy-terminal segment of p53 can mediate repression
when bound to DNA as a GAL4-p53 fusion protein. The amino- and
carboxy-terminal p53 interactions occur within the domain on the
TATA-binding protein to which the adenovirus 13S E1A oncoprotein has
previously been shown to bind. The 13S E1A oncoprotein can dissociate the
complex formed between the carboxy-terminal domain of p53 and the
TATA-binding protein and relieve p53-mediated transcriptional repression.
These results demonstrate that two independent domains of p53 can
potentially interact with the TATA-binding protein, and they define a
mechanism-- relief of repression--by which the 13S E1A oncoprotein can
activate transcription through the TATA motif.
Copyright © 1995, American Society for Microbiology
Two domains of p53 interact with the TATA-binding protein, and the adenovirus 13S E1A protein disrupts the association, relieving p53- mediated transcriptional repression
Department of Molecular Biology, Howard Hughes Medical Institute, Princeton University, New Jersey 08544-1014.
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