title: Activation of p53-dependent responses in tumor cells treated with a PARC-interacting peptide.
abstract: We tested the activity of a p53 carboxy-terminal peptide containing the PARC-interacting region in cancer cells with wild type cytoplasmic p53. Peptide delivery was achieved by fusing it to the TAT transduction domain (TAT-p53-C-ter peptide). In a two-hybrid assay, the tetramerization domain (TD) of p53 was necessary and sufficient to bind PARC. The TAT-p53-C-ter peptide disrupted the PARC-p53 complex. Peptide treatment caused p53 nuclear relocation, p53-dependent changes in gene expression and enhancement of etoposide-induced apoptosis. These studies suggest that PARC-interacting peptides are promising candidates for the enhancement of p53-dependent apoptosis in tumors with wt cytoplasmic p53.
authors.affiliation: ENEA Research Center Casaccia, Section of Toxicology and Biomedical Sciences, Via Anguillarese, 301, Rome 00123, Italy.
authors.forename: Roberta
authors.initials: R
authors.lastname: Vitali
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Cesi
authors.forename: Barbara
authors.initials: B
authors.lastname: Tanno
authors.forename: Giovanna
authors.initials: G
authors.lastname: Ferrari-Amorotti
authors.forename: Carlo
authors.initials: C
authors.lastname: Dominici
authors.forename: Bruno
authors.initials: B
authors.lastname: Calabretta
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Raschellà
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D045744:Cell Line, Tumor; D027101:DNA Topoisomerase IV / Q000008:administration & dosage*; D006801:Humans; D009369:Neoplasms / Q000378:metabolism* / Q000473:pathology*; D015398:Signal Transduction / Q000187:drug effects*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
chemical_list: C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D027101:DNA Topoisomerase IV