p73γ transactivates the p21 promoter through preferential interaction with the p300/CBP-associated factor in human prostate cancer cells

Abstract

Several p73 variants have been reported with different carboxy-terminal structures and transcriptional activities. We showed that p73γ had stronger transactivation activity than the other splicing variants such as α, β and δ by analysing p21 promoter activity in human prostate cancer PC3 cells. The transactivation activity of p73γ was similar to that of p53 and was enhanced by co-transfection with p300/CBP-associated factor (PCAF). In vitro pull-down assay, p73 variants were able to bind to PCAF with a similar extent. However, in vivo co-immunoprecipitation assays showed that p73γ interacted preferentially with PCAF. Neither in vitro-translated nor in vivo-immunoprecipitated p73γ were able to bind to oligonucleotides containing the p53 consensus binding site. However, p73γ acetylated by PCAF restored DNA binding activity. Differential functions of p73 variants are supposed to be regulated by the structural differences of carboxy-terminal region. Our results revealed that p21 promoter activity was affected by differential interactions of p73 variants with PCAF and its acetylation.