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Molecular and Cellular Biology, February 1999, p. 1202-1209, Vol. 19, No. 2
The Wistar Institute, Philadelphia,
Pennsylvania 19104
Received 18 August 1998/Returned for modification 2 October
1998/Accepted 4 November 1998
The p53 tumor suppressor protein is a sequence-specific
transcription factor that modulates the response of cells to DNA
damage. Recent studies suggest that full transcriptional activity of
p53 requires the coactivators CREB binding protein (CBP)/p300 and PCAF.
These coactivators interact with each other, and both possess intrinsic
histone acetyltransferase activity. Furthermore, p300 acetylates p53 to
activate its sequence-specific DNA binding activity in vitro. In this
study, we demonstrate that PCAF also acetylates p53 in vitro at a
lysine residue distinct from that acetylated by p300 and thereby
increases p53's ability to bind to its cognate DNA site. We have
generated antibodies to acetylated p53 peptides at either of the two
lysine residues that are targeted by PCAF or p300 and have demonstrated
that these antibodies are highly specific for both acetylation and the
particular site. Using these antibodies, we detect acetylation of these
sites in vivo, and interestingly, acetylation at both sites increases
in response to DNA-damaging agents. These data indicate that
site-specific acetylation of p53 increases under physiological
conditions that activate p53 and identify CBP/p300 and PCAF as the
probable enzymes that modify p53 in vivo.
0270-7306/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.
p53 Sites Acetylated In Vitro by PCAF and p300 Are
Acetylated In Vivo in Response to DNA Damage
*
Corresponding author. Mailing address for Shelley L. Berger: The Wistar Institute, 3601 Spruce St., Philadelphia, PA 19104. Phone: (215) 898-3922. Fax: (215) 898-0663. E-mail:
berger{at}wista.wistar.upenn.edu. Mailing address for
Thomas D. Halazonetis: The Wistar Institute, 3601 Spruce St.,
Philadelphia, PA 19104. Phone: (215) 898-3978. Fax: (215) 898-3868. E-mail: halazonetis{at}wista.wistar.upenn.edu.
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