Activation of the tumor-specific death effector apoptin and its kinase by an N-terminal determinant of simian virus 40 large T antigen
| Autor: | Mathieu H.M. Noteborn, Jennifer L. Rohn, Klaas Kooistra, Alexandra Maria Pietersen, Ying-Hui Zhang |
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| Rok vydání: | 2004 |
| Předmět: |
Antigens
Polyomavirus Transforming Immunology Apoptosis Simian virus 40 Biology Microbiology Cell Line Mice Antigen Virology medicine NLS Animals Humans Amino Acid Sequence Cell Nucleus Kinase Cell Transformation Viral Cell biology Protein Structure Tertiary Virus-Cell Interactions Cell nucleus medicine.anatomical_structure Cell Transformation Neoplastic Viral replication Insect Science Mutation Phosphorylation Capsid Proteins Nuclear localization sequence Chicken anemia virus |
| Zdroj: | Journal of virology. 78(18) |
| ISSN: | 0022-538X |
| Popis: | Apoptin, a viral death protein derived from chicken anemia virus, displays a number of tumor-specific behaviors. In particular, apoptin is phosphorylated, translocates to the nucleus, and induces apoptosis specifically in tumor or transformed cells, whereas it is nonphosphorylated and remains primarily inactive in the cytoplasm of nontransformed normal cells. Here, we show that in normal cells apoptin can also be activated by the transient transforming signals conferred by ectopically expressed simian virus 40 (SV40) large T antigen (LT), which rapidly induces apoptin's phosphorylation, nuclear accumulation, and the ability to induce apoptosis. Further analyses with mutants of LT showed that the minimum domain capable of inducing all three of apoptin's tumor-specific properties resided in the N-terminal J domain, a sequence which is largely shared by SV40 small t antigen (st). Interestingly, the J domain in st, which lacks its own nuclear localization signal (NLS), required nuclear localization to activate apoptin. These results reveal the existence of a cellular pathway shared by conditions of transient transformation and the stable cancerous or precancerous state, and they support a model whereby a transient transforming signal confers on apoptin both the upstream activity of phosphorylation and the downstream activity of nuclear accumulation and apoptosis induction. Such a pathway may reflect a general lesion contributing to human cancers. |
| Databáze: | OpenAIRE |
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