The acetyltransferase p300/CBP-associated factor is a p53 target gene in breast tumor cells.
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.
Watts
George S
GS
Bone Marrow Transplant Program, Arizona Cancer Center and Department of Pharmacology and Toxicology, University of Arizona, Tucson, AZ 85724, USA. gwatts@azcc.arizona.edu
Oshiro
Marc M
MM
Junk
Damian J
DJ
Wozniak
Ryan J
RJ
Watterson
Summer
S
Domann
Frederick E
FE
Futscher
Bernard W
BW
D000123:Acetyltransferases / Q000235:genetics* / Q000378:metabolism*; D000256:Adenoviridae / Q000235:genetics; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism*; D018797:Cell Cycle Proteins / Q000235:genetics* / Q000378:metabolism*; D045744:Cell Line, Tumor; D004317:Doxorubicin / Q000494:pharmacology; D015972:Gene Expression Regulation, Neoplastic; D005822:Genetic Vectors / Q000235:genetics; D051548:Histone Acetyltransferases; D006801:Humans; D020411:Oligonucleotide Array Sequence Analysis; D011401:Promoter Regions, Genetic / Q000235:genetics; D011485:Protein Binding; D034741:RNA, Small Interfering / Q000235:genetics; D014157:Transcription Factors; D014162:Transfection; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*; D050880:p300-CBP Transcription Factors; D000099224:p300-CBP-Associated Factor
D000123:Acetyltransferases; D018797:Cell Cycle Proteins; D004317:Doxorubicin; D051548:Histone Acetyltransferases; D034741:RNA, Small Interfering; D014157:Transcription Factors; D016159:Tumor Suppressor Protein p53; D050880:p300-CBP Transcription Factors; D000099224:p300-CBP-Associated Factor