The Acetyltransferase p300/CBP-Associated Factor Is a p53 Target Gene in Breast Tumor Cells

George S Watts; Marc M Oshiro; Damian J Junk; Ryan J Wozniak; Summer J Watterson; Frederick E Domann; Bernard W Futscher

doi:10.1593/neo.03292

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The Acetyltransferase p300/CBP-Associated Factor Is a p53 Target Gene in Breast Tumor Cells

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The Acetyltransferase p300/CBP-Associated Factor Is a p53 Target Gene in Breast Tumor Cells

George S Watts, Marc M Oshiro, Damian J Junk, Ryan J Wozniak, Summer J Watterson, Frederick E Domann and Bernard W Futscher

Neoplasia (New York, N.Y.), Vol.6(3), pp.187-194

05/2004

DOI: 10.1593/neo.03292

PMID: 15153330

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Abstract

p300/CBP-associated factor (PCAF) is a coactivator of the tumor suppressor, p53. PCAF participates in p53's transactivation of target genes through acetylation of both bound p53 and histones within p53 target promoters. Using microarrays, we discovered that PCAF itself is induced by p53 in a panel of breast tumor cell lines. Two p53 mutant breast tumor cell lines, BT-549 and UACC-1179, were chosen for further study of PCAF induction by wild-type p53. PCAF induction following adenoviral transduction of p53 expression was confirmed with real-time polymerase chain reaction in a time course experiment. Chromatin immunoprecipitation experiments then showed that PCAF induction was associated with increased p53 binding to the PCAF promoter, which contains p53 consensus-binding sites. PCAF induction by p53 activity was further demonstrated in wild-type p53 MCF10A cells when PCAF expression was induced following activation of endogenous wild-type p53 with doxorubicin in a dose- and time-dependent manner. Furthermore, the doxorubicin-induced increase in PCAF expression was blocked by pretreatment of the MCF10A cells with siRNA (small interfering RNA) targeted against p53 mRNA. Taken together, the results show that PCAF expression can be induced by wild-type p53.

p53, PCAF

Microarray

p300/CBP-associated factor

acetyltransferase

Details

Title: Subtitle: The Acetyltransferase p300/CBP-Associated Factor Is a p53 Target Gene in Breast Tumor Cells
Creators: George S Watts - Bone Marrow Transplant Program, Arizona Cancer Center and Department of Pharmacology and Toxicology, University of Arizona, Tucson, AZ 85724, USA
Marc M Oshiro - Bone Marrow Transplant Program, Arizona Cancer Center and Department of Pharmacology and Toxicology, University of Arizona, Tucson, AZ 85724, USA
Damian J Junk - Bone Marrow Transplant Program, Arizona Cancer Center and Department of Pharmacology and Toxicology, University of Arizona, Tucson, AZ 85724, USA
Ryan J Wozniak - Bone Marrow Transplant Program, Arizona Cancer Center and Department of Pharmacology and Toxicology, University of Arizona, Tucson, AZ 85724, USA
Summer J Watterson - Bone Marrow Transplant Program, Arizona Cancer Center and Department of Pharmacology and Toxicology, University of Arizona, Tucson, AZ 85724, USA
Frederick E Domann - Department of Radiology, Free Radical and Radiation Biology Program, College of Medicine, University of Iowa and the Iowa Cancer Center, Iowa City, IA 52242, USA
Bernard W Futscher - Bone Marrow Transplant Program, Arizona Cancer Center and Department of Pharmacology and Toxicology, University of Arizona, Tucson, AZ 85724, USA
Resource Type: Journal article
Publication Details: Neoplasia (New York, N.Y.), Vol.6(3), pp.187-194
DOI: 10.1593/neo.03292
PMID: 15153330
NLM abbreviation: Neoplasia
ISSN: 1476-5586
eISSN: 1476-5586
Publisher: Elsevier Inc
Language: English
Date published: 05/2004
Academic Unit: Pathology; Surgery; Radiation Oncology
Record Identifier: 9984047686302771

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