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

Research output: Contribution to journalArticle

35 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)187-194
Number of pages8
JournalNeoplasia
Volume6
Issue number3
StatePublished - May 2004

Fingerprint

Acetyltransferases
p53 Genes
Breast Neoplasms
Tumor Cell Line
Doxorubicin
p300-CBP-associated factor
Chromatin Immunoprecipitation
Acetylation
Histones
Small Interfering RNA
Transcriptional Activation
Real-Time Polymerase Chain Reaction
Binding Sites

Keywords

  • Acetyltransferase
  • Microarray
  • P300/CBP-associated factor
  • P53
  • PCAF

ASJC Scopus subject areas

  • Cancer Research

Cite this

Watts, G. S., Oshiro, M. M., Junk, D. J., Wozniak, R. J., Watterson, S. J., Domann, F. E., & Futscher, B. W. (2004). The acetyltransferase p300/CBP-associated factor is a p53 target gene in breast tumor cells. Neoplasia, 6(3), 187-194.

The acetyltransferase p300/CBP-associated factor is a p53 target gene in breast tumor cells. / Watts, George S; Oshiro, Marc M.; Junk, Damian J.; Wozniak, Ryan J.; Watterson, Summer J.; Domann, Frederick E.; Futscher, Bernard W.

In: Neoplasia, Vol. 6, No. 3, 05.2004, p. 187-194.

Research output: Contribution to journalArticle

Watts, GS, Oshiro, MM, Junk, DJ, Wozniak, RJ, Watterson, SJ, Domann, FE & Futscher, BW 2004, 'The acetyltransferase p300/CBP-associated factor is a p53 target gene in breast tumor cells', Neoplasia, vol. 6, no. 3, pp. 187-194.
Watts GS, Oshiro MM, Junk DJ, Wozniak RJ, Watterson SJ, Domann FE et al. The acetyltransferase p300/CBP-associated factor is a p53 target gene in breast tumor cells. Neoplasia. 2004 May;6(3):187-194.
Watts, George S ; Oshiro, Marc M. ; Junk, Damian J. ; Wozniak, Ryan J. ; Watterson, Summer J. ; Domann, Frederick E. ; Futscher, Bernard W. / The acetyltransferase p300/CBP-associated factor is a p53 target gene in breast tumor cells. In: Neoplasia. 2004 ; Vol. 6, No. 3. pp. 187-194.
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