1. Simian Virus 40 Large Tumor Antigen Modulates the Raf Signaling Pathway
- Author
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Adina Vultur, Aliki Siganou, Leda Raptis, Heather L. Brownell, Thomas M. Roberts, Nicholas Grammatikakis, Christian Rausch, Ole Gjoerup, Katarzyna Jaronczyk, Renée Lapointe, and Marc Benzaquen
- Subjects
Insecta ,Large tumor ,Antigens, Polyomavirus Transforming ,Down-Regulation ,Simian ,Transfection ,Biochemistry ,Virus ,Cell Line ,law.invention ,Mice ,Antigen ,law ,Catalytic Domain ,medicine ,Animals ,Humans ,Phosphorylation ,Molecular Biology ,biology ,Oncogene ,Cell Biology ,Fibroblasts ,biology.organism_classification ,Precipitin Tests ,Virology ,Protein Structure, Tertiary ,Cell biology ,Enzyme Activation ,Proto-Oncogene Proteins c-raf ,Genes, ras ,Phenotype ,Mechanism of action ,ras Proteins ,Suppressor ,Signal transduction ,medicine.symptom ,Protein Binding ,Signal Transduction - Abstract
The large tumor antigen of simian virus 40 (SVLT) is a potent oncogene. Although inactivation of the p53 and pRb tumor suppressors has been causally linked to the transforming properties of SVLT, its exact mechanism of action remains undefined. Previous data indicated that Ras is activated in SVLT-expressing cells. In this report we show that SVLT also increases Raf kinase activity in both insect and mammalian cells, thus identifying the Raf kinase as an additional target of SVLT. Our results further show that SVLT was still able to activate Raf in cells where Ras levels had been drastically reduced through expression of an antisense construct, indicating that SVLT may activate Raf at least partly by a mechanism that is independent of its stimulatory effect on Ras.
- Published
- 2001
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