Importance of nuclear localization of apoptin for tumor-specific induction of apoptosis

Danen-van Oorschot, Astrid A. A. M. and Zhang, Ying-Hui and Leliveld, S. Rutger and Rohn, Jennifer L. and Seelen, Maud C. M. J. and Bolk, Marian W. and van Zon, Arend and Erkeland, Stefan J. and Abrahams, Jan-Pieter and Mumberg, Dominik and Noteborn, Mathieu H. M.. (2003) Importance of nuclear localization of apoptin for tumor-specific induction of apoptosis. Journal of Biological Chemistry, 278 (30). pp. 27729-27736.

Full text not available from this repository.

Official URL: https://edoc.unibas.ch/75974/

Downloads: Statistics Overview


The chicken anemia virus-derived protein Apoptin induces apoptosis specifically in human tumor and transformed cells and not in normal, untransformed cells. The cell killing activity correlates with a predominantly nuclear localization of Apoptin in tumor cells, whereas in normal cells, it is detected mainly in cytoplasmic structures. To explore the role of nuclear localization for Apoptin-induced cell death in tumor cells, we employed a mutagenesis strategy. First, we demonstrated that the C terminus of Apoptin contains a bipartite-type nuclear localization signal. Strikingly, further investigation showed that Apoptin contains two different domains that induce apoptosis independently, and for both domains, we found a strong correlation between localization and killing activity. Using inhibitors, we ruled out the involvement of de novo gene transcription and translation and further showed that Apoptin itself does not have any significant transcriptional repression activity, suggesting that Apoptin exerts its effects in the nucleus by some other method. To determine whether nuclear localization is sufficient to enable Apoptin to kill normal, untransformed cells, we expressed full-length Apoptin fused to a heterologous nuclear localization signal in these cells. However, despite its nuclear localization, no apoptosis was induced, which suggests that nuclear localization per se is not sufficient for Apoptin to become active. These studies increase our understanding of the molecular pathway of Apoptin and may also shed light on the mechanism of cellular transformation.
Faculties and Departments:05 Faculty of Science > Departement Biozentrum > Structural Biology & Biophysics > Nano-diffraction of Biological Specimen (Abrahams)
UniBasel Contributors:Abrahams, Jan Pieter
Item Type:Article, refereed
Article Subtype:Research Article
Publisher:American Society for Biochemistry and Molecular Biology
Note:Publication type according to Uni Basel Research Database: Journal article
Identification Number:
Last Modified:05 Nov 2020 15:52
Deposited On:05 Nov 2020 15:52

Repository Staff Only: item control page