title: Activating transcription factor 3 is crucial for antitumor activity and to strengthen the antiviral properties of Onconase.
abstract: Onconase is a ribonuclease that presents both antitumor and antiviral properties linked to its ribonucleolytic activity and represents a new class of RNA-damaging drugs. It has reached clinical trials for the treatment of several cancers and human papilloma virus warts. Onconase targets different RNAs in the cell cytosol but Onconase-treated cells present features that are different from a simple arrest of protein synthesis. We have used microarray-derived transcriptional profiling to identify Onconase-regulated genes in two ovarian cancer cell lines (NCI/ADR-RES and OVCAR-8). RT-qPCR analyses have confirmed the microarray findings. We have identified a network of up-regulated genes implicated in different signaling pathways that may explain the cytotoxic effects exerted by Onconase. Among these genes, activating transcription factor 3 (ATF3) plays a central role in the key events triggered by Onconase in treated cancer cells that finally lead to apoptosis. This mechanism, mediated by ATF3, is cell-type independent. Up-regulation of ATF3 may also explain the antiviral properties of this ribonuclease because this factor is involved in halting viral genome replication, keeping virus latency or preventing viral oncogenesis. Finally, Onconase-regulated genes are different from those affected by nuclear-directed ribonucleases.
authors.affiliation: Laboratori d'Enginyeria de Proteïnes, Departament de Biologia, Facultat de Ciències, Universitat de Girona, Campus de Montilivi, 17003, Girona, Spain.|Institut d'Investigació Biomèdica de Girona Josep Trueta, (IdIBGi), Girona, Spain.
authors.forename: Anna
authors.initials: A
authors.lastname: Vert
authors.affiliation: Laboratori d'Enginyeria de Proteïnes, Departament de Biologia, Facultat de Ciències, Universitat de Girona, Campus de Montilivi, 17003, Girona, Spain.|Institut d'Investigació Biomèdica de Girona Josep Trueta, (IdIBGi), Girona, Spain.
authors.forename: Jessica
authors.initials: J
authors.lastname: Castro
authors.affiliation: Laboratori d'Enginyeria de Proteïnes, Departament de Biologia, Facultat de Ciències, Universitat de Girona, Campus de Montilivi, 17003, Girona, Spain.|Institut d'Investigació Biomèdica de Girona Josep Trueta, (IdIBGi), Girona, Spain.
authors.forename: Marc
authors.initials: M
authors.lastname: Ribó
authors.affiliation: Laboratori d'Enginyeria de Proteïnes, Departament de Biologia, Facultat de Ciències, Universitat de Girona, Campus de Montilivi, 17003, Girona, Spain.|Institut d'Investigació Biomèdica de Girona Josep Trueta, (IdIBGi), Girona, Spain.
authors.forename: Antoni
authors.initials: A
authors.lastname: Benito
authors.affiliation: Laboratori d'Enginyeria de Proteïnes, Departament de Biologia, Facultat de Ciències, Universitat de Girona, Campus de Montilivi, 17003, Girona, Spain.|Institut d'Investigació Biomèdica de Girona Josep Trueta, (IdIBGi), Girona, Spain.
authors.forename: Maria
authors.initials: M
authors.lastname: Vilanova
mesh_terms: D051700:Activating Transcription Factor 3 / Q000096:biosynthesis / Q000235:genetics*; D000970:Antineoplastic Agents / Q000494:pharmacology*; D000998:Antiviral Agents / Q000494:pharmacology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D020411:Oligonucleotide Array Sequence Analysis; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000378:metabolism; D012260:Ribonucleases / Q000494:pharmacology*
chemical_list: C490449:ATF3 protein, human; D051700:Activating Transcription Factor 3; D000970:Antineoplastic Agents; D000998:Antiviral Agents; D012260:Ribonucleases; C058703:ranpirnase
keywords: Onconase; activating transcription factor 3; antitumor and antiviral drug; apoptosis; microarray profiling