Domenico Narciso

Publications (2)10.24 Total impact

• Source

  Available from: Enrico Iaccino

  Article: Isolation and Functional Characterization of Peptide Agonists of PTPRJ, a Tyrosine Phosphatase Receptor Endowed with Tumor Suppressor Activity.

  Francesco Paduano, Francesco Ortuso, Pietro Campiglia, Cinzia Raso, Enrico Iaccino, Marco Gaspari, Eugenio Gaudio, Graziella Mangone, Alfonso Carotenuto, Anna Bilotta, [......], Giovanni Cuda, Rodolfo Iuliano, Nicola Perrotti, Giuseppe Scala, Giuseppe Viglietto, Stefano Alcaro, Carlo M Croce, Ettore Novellino, Alfredo Fusco, Francesco Trapasso
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  ABSTRACT: PTPRJ is a receptor-type protein tyrosine phosphatase whose expression is strongly reduced in the majority of investigated cancer cell lines and tumor specimens. PTPRJ negatively interferes with mitogenic signals originating from several oncogenic receptor tyrosine kinases, including HGFR, PDGFR, RET, and VEGFR-2. Here we report the isolation and characterization of peptides from a random peptide phage display library that bind and activate PTPRJ. These agonist peptides, which are able to both circularize and form dimers in acqueous solution, were assayed for their biochemical and biological activity on both human cancer cells and primary endothelial cells (HeLa and HUVEC, respectively). Our results demonstrate that binding of PTPRJ-interacting peptides to cell cultures dramatically reduces the extent of both MAPK phosphorylation and total phosphotyrosine levels; conversely, they induce a significant increase of the cell cycle inhibitor p27(Kip1). Moreover, PTPRJ agonist peptides both reduce proliferation and trigger apoptosis of treated cells. Our data indicate that peptide agonists of PTPRJ positively modulate the PTPRJ activity and may lead to novel targeted anticancer therapies.
  ACS Chemical Biology 07/2012; 7(10):1666-76. · 6.45 Impact Factor
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  Available from: Rodolfo Iuliano

  Article: Protein tyrosine phosphatase PTPRJ is negatively regulated by microRNA-328.

  Francesco Paduano, Vincenzo Dattilo, Domenico Narciso, Anna Bilotta, Eugenio Gaudio, Miranda Menniti, Valter Agosti, Camillo Palmieri, Nicola Perrotti, Alfredo Fusco, Francesco Trapasso, Rodolfo Iuliano
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  ABSTRACT: Expression of PTPRJ, which is a ubiquitous receptor-type protein tyrosine phosphatase, is significantly reduced in a vast majority of human epithelial cancers and cancer cell lines (i.e. colon, lung, thyroid, mammary and pancreatic tumours). A possible role for microRNAs (miRNAs) in the negative regulation of PTPRJ expression has never been investigated. In this study, we show that overexpression of microRNA-328 (miR-328) decreases PTPRJ expression in HeLa and SKBr3 cells. Further investigations demonstrate that miR-328 acts directly on the 3'UTR of PTPRJ, resulting in reduced mRNA levels. Luciferase assay and site-specific mutagenesis were used to identify a functional miRNA response element in the 3'UTR of PTPRJ. Expression of miR-328 significantly enhances cell proliferation in HeLa and SKBr3 cells, similar to the effects of downregulation of PTPRJ with small interfering RNA. Additionally, in HeLa cells, the proliferative effect of miR-328 was not observed when PTPRJ was silenced with small interfering RNA; conversely, restoration of PTPRJ expression in miR-328-overexpressing cells abolished the proliferative activity of miR-328. In conclusion, we report the identification of miR-328 as an important player in the regulation of PTPRJ expression, and we propose that the interaction of miR-328 with PTPRJ is responsible for miR-328-dependent increase of epithelial cell proliferation.
  FEBS Journal 05/2012; · 3.79 Impact Factor