TY - JOUR
T1 - The acetyltransferase p300/CBP-associated factor is a p53 target gene in breast tumor cells
AU - Watts, George S.
AU - Oshiro, Marc M.
AU - Junk, Damian J.
AU - Wozniak, Ryan J.
AU - Watterson, Summer J.
AU - Domann, Frederick E.
AU - Futscher, Bernard W.
N1 - Funding Information:
Abbreviations: ChIP, chromatin immunoprecipitation; PCAF, p300/CBP–associated factor; RT–PCR, reverse transcription–polymerase chain reaction; siRNA, small interfering RNA; GFP, green fluorescent protein Address all correspondence to: George S. Watts, Arizona Cancer Center, 1515 North Campbell Avenue, Tucson, AZ 85724, USA. E-mail: [email protected] 1This work was supported by grants CA65662 to B.W.F., NIH 73612 to F.E.D., 3P30 CA23074-19 to the Arizona Cancer Center, and ES06694 to the Southwest Environmental Health Sciences Center. M.O. was supported by a Cancer Biology Training grant from the National Institutes of Health. R.J.W. received support from a NIEHS Toxicology Training grant. Received 25 August 2003; Revised 6 January 2004; Accepted 7 January 2004.
PY - 2004
Y1 - 2004
N2 - 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.
AB - 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.
KW - Acetyltransferase
KW - Microarray
KW - P300/CBP-associated factor
KW - P53
KW - PCAF
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U2 - 10.1593/neo.3292
DO - 10.1593/neo.3292
M3 - Article
C2 - 15153330
AN - SCOPUS:2442672704
SN - 1522-8002
VL - 6
SP - 187
EP - 194
JO - Neoplasia
JF - Neoplasia
IS - 3
ER -