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Activation of p53-dependent responses in tumor cells treated with a PARC-interacting peptide |
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| Authors: | Vitali Roberta Cesi Vincenzo Tanno Barbara Ferrari-Amorotti Giovanna Dominici Carlo Calabretta Bruno Raschellà Giuseppe |
| Affiliation: | a ENEA Research Center Casaccia, Section of Toxicology and Biomedical Sciences, Via Anguillarese, 301, Rome 00123, Italy b Department of Biomedical Sciences, University of Modena, Modena, Italy c Department of Pediatrics, La Sapienza University, Rome, Italy d Laboratory of Oncology, Bambino Gesù Children’s Hospital, Rome, Italy e Division of Child Health, School of Reproductive and Developmental Medicine, Liverpool University, Liverpool, UK f Kimmel Cancer Center, Thomas Jefferson University, 233 South 10th Street, Philadelphia, PA 19107, USA |
| 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. |
| Keywords: | p53 PARC TAT Apoptosis Etoposide |
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