title: Apoptin: therapeutic potential of an early sensor of carcinogenic transformation.
abstract: The avian virus-derived protein apoptin induces p53-independent apoptosis in a tumor-specific way. Apoptin acts as a multimeric complex and forms superstructures upon binding to DNA. In tumor cells, apoptin is phosphorylated and mainly nuclear, whereas in normal cells it is unphosphorylated, cytoplasmic, and becomes readily neutralized. Interestingly, apoptin phosphorylation, nuclear translocation, and apoptosis can transiently be induced in normal cells by cotransfecting SV40 large T oncogene, indicating that apoptin recognizes early stages of oncogenic transformation. In cancer cells, apoptin appears to recognize survival signals, which it is able to redirect into cell death impulses. Apoptin targets include DEDAF, Nur77, Nmi, Hippi, and the potential drug target APC1. Apoptin-transgenic mice and animal tumor models have revealed apoptin as a safe and efficient antitumor agent, resulting in significant tumor regression. Future antitumor therapies could use apoptin either as a therapeutic bullet or as an early sensor of druggable tumor-specific processes.
authors.affiliation: Molecular Genetics, Leiden Institute of Chemistry, Leiden University, Leiden, The Netherlands. backendo@chem.leidenuniv.nl
authors.forename: Claude
authors.initials: C
authors.lastname: Backendorf
authors.forename: Astrid E
authors.initials: AE
authors.lastname: Visser
authors.forename: A G
authors.initials: AG
authors.lastname: de Boer
authors.forename: Rhyenne
authors.initials: R
authors.lastname: Zimmerman
authors.forename: Mijke
authors.initials: M
authors.lastname: Visser
authors.forename: Patrick
authors.initials: P
authors.lastname: Voskamp
authors.forename: Ying-Hui
authors.initials: YH
authors.lastname: Zhang
authors.forename: Mathieu
authors.initials: M
authors.lastname: Noteborn
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000378:metabolism / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D036022:Capsid Proteins / Q000378:metabolism / Q000494:pharmacology*; D002471:Cell Transformation, Neoplastic / Q000378:metabolism; D004195:Disease Models, Animal; D016503:Drug Delivery Systems; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy*
chemical_list: D000970:Antineoplastic Agents; D036022:Capsid Proteins; C091717:VP3 protein, Chicken anemia virus