title: A truncated apoptin protein variant selectively kills cancer cells.
abstract: Apoptin is a nonstructural protein encoded by one of the three open reading frames of the chicken anemia virus genome. It has attracted a great deal of interest due to its ability to induce apoptosis in multiple transformed and malignant mammalian cell lines without affecting primary and non-transformed cells. However, the use of Apoptin as an anticancer drug is restricted by its strong tendency to aggregate. A number of methods to overcome this problem have been proposed, including transduction techniques to deliver the Apoptin gene into tumor cells, but all such methods have certain drawbacks. Here we describe that a truncated variant of Apoptin, lacking residues 1 to 43, is a soluble, non-aggregating protein that maintains most of the biological properties of wild-type Apoptin when transfected into cells. We show that the cytotoxic effect of this variant is also present when it is added exogenously to cancer cells, but not to normal cells. In addition to the interest this protein has attracted as a promising therapeutic strategy, it is also an excellent model to study the structural properties of Apoptin and how they relate to its mechanism of action.
authors.affiliation: Laboratori d'Enginyeria de Proteïnes, Departament de Biologia, Facultat de Ciències, Universitat de Girona and Institut d'Investigació Biomèdica de Girona Josep Trueta (IdIBGi), Girona, Spain.
authors.forename: Santiago
authors.initials: S
authors.lastname: Ruiz-Martínez
authors.affiliation: Laboratori d'Enginyeria de Proteïnes, Departament de Biologia, Facultat de Ciències, Universitat de Girona and 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 and Institut d'Investigació Biomèdica de Girona Josep Trueta (IdIBGi), Girona, Spain.
authors.forename: Maria
authors.initials: M
authors.lastname: Vilanova
authors.affiliation: Instituto de Química Física "Rocasolano", Consejo Superior de Investigaciones Científicas, Serrano 119, 28006, Madrid, Spain.
authors.forename: Marta
authors.initials: M
authors.lastname: Bruix
authors.affiliation: Instituto de Química Física "Rocasolano", Consejo Superior de Investigaciones Científicas, Serrano 119, 28006, Madrid, Spain.
authors.forename: Douglas V
authors.initials: DV
authors.lastname: Laurents
authors.affiliation: Laboratori d'Enginyeria de Proteïnes, Departament de Biologia, Facultat de Ciències, Universitat de Girona and 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 and Institut d'Investigació Biomèdica de Girona Josep Trueta (IdIBGi), Girona, Spain. antoni.benito@udg.edu.
authors.forename: Antoni
authors.identifier: 0000-0002-9776-1003
authors.initials: A
authors.lastname: Benito
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D036022:Capsid Proteins / Q000737:chemistry* / Q000235:genetics / Q000494:pharmacology*; D002460:Cell Line; D045744:Cell Line, Tumor; D004247:DNA / Q000378:metabolism; D004926:Escherichia coli / Q000235:genetics; D006801:Humans; D014162:Transfection
chemical_list: D000970:Antineoplastic Agents; D036022:Capsid Proteins; C091717:VP3 protein, Chicken anemia virus; D004247:DNA
keywords: Aggregation; Anticancer drug; Apoptin; Protein engineering; Viral protein