Abstract
Several p73 variants have been reported with different carboxy-terminal structures and transcriptional activities. We showed that p73gamma had stronger transactivation activity than the other splicing variants such as alpha, beta and delta by analysing p21 promoter activity in human prostate cancer PC3 cells. The transactivation activity of p73gamma 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 p73gamma interacted preferentially with PCAF. Neither in vitro-translated nor in vivo-immunoprecipitated p73gamma were able to bind to oligonucleotides containing the p53 consensus binding site. However, p73gamma 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.
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Acetylation
-
Alternative Splicing
-
Binding Sites / genetics
-
Blotting, Western
-
Cell Cycle Proteins / genetics
-
Cell Cycle Proteins / metabolism*
-
Cell Line, Tumor
-
Cyclin-Dependent Kinase Inhibitor p21 / genetics
-
DNA-Binding Proteins / genetics
-
DNA-Binding Proteins / metabolism*
-
Electrophoretic Mobility Shift Assay
-
Histone Acetyltransferases / genetics
-
Histone Acetyltransferases / metabolism*
-
Humans
-
Immunoprecipitation
-
Luciferases / genetics
-
Luciferases / metabolism
-
Male
-
Mutation
-
Nuclear Proteins / genetics
-
Nuclear Proteins / metabolism*
-
Oligonucleotides / genetics
-
Oligonucleotides / metabolism
-
Promoter Regions, Genetic / genetics
-
Prostatic Neoplasms / genetics
-
Prostatic Neoplasms / metabolism
-
Prostatic Neoplasms / pathology
-
Protein Binding
-
Protein Isoforms / genetics
-
Protein Isoforms / metabolism
-
Transcription Factors / genetics
-
Transcription Factors / metabolism*
-
Transcriptional Activation
-
Transfection
-
Tumor Protein p73
-
Tumor Suppressor Protein p53 / metabolism
-
Tumor Suppressor Proteins / genetics
-
Tumor Suppressor Proteins / metabolism*
-
p300-CBP Transcription Factors
Substances
-
Cell Cycle Proteins
-
Cyclin-Dependent Kinase Inhibitor p21
-
DNA-Binding Proteins
-
Nuclear Proteins
-
Oligonucleotides
-
Protein Isoforms
-
TP73 protein, human
-
Transcription Factors
-
Tumor Protein p73
-
Tumor Suppressor Protein p53
-
Tumor Suppressor Proteins
-
Luciferases
-
Histone Acetyltransferases
-
p300-CBP Transcription Factors
-
p300-CBP-associated factor