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Phosphorylation of bovine leukemia virus Tax protein is required for in vitro transformation but not for transactivation.

التفاصيل البيبلوغرافية
العنوان: Phosphorylation of bovine leukemia virus Tax protein is required for in vitro transformation but not for transactivation.
المؤلفون: Willems, Luc, Grimonpont, Cathy, Kerkhofs, Pierre, Capiau, Carine, Gheysen, Dirk, Conrath, Karel, Roussef, Roussi, Mamoun, Robert, Portetelle, Daniel, Burny, Arsène, Adam, Emmanuelle, Lefebvre, Laurent, Twizere, Jean-Claude, Heremans, Hubertine, Kettmann, Richard
المصدر: Oncogene, 16 (17), 2165-76 (1998)
بيانات النشر: Nature Publishing Group
سنة النشر: 1998
المجموعة: University of Liège: ORBi (Open Repository and Bibliography)
مصطلحات موضوعية: Animals, CDC2 Protein Kinase/metabolism, Calcium-Calmodulin-Dependent Protein Kinases/metabolism, Cattle, Cell Line, Cell Transformation, Viral/genetics, Fibroblasts, Gene Products, tax/antagonists & inhibitors/genetics/metabolism, Leukemia Virus, Bovine/genetics/physiology, Mice, Nude, Mutagenesis, Site-Directed, Phosphorylation, Rats, Inbred F344, Serine/genetics/metabolism, Spodoptera, Transcriptional Activation/physiology, Virus Replication/genetics, Life sciences, Biochemistry, biophysics & molecular biology, Sciences du vivant, Biochimie, biophysique & biologie moléculaire
الوصف: peer reviewed ; The Tax proteins of the oncovirinae viruses are phosphorylated transcriptional activators that exhibit oncogenic potential. The role of phosphorylation in their functional activities remains unknown. As a model for the Human T-cell leukemia virus type I (HTLV-I), Bovine Leukemia Virus (BLV) permits the characterization of viral replication and leukemogenesis in vivo. Here, we show that the BLV Tax protein is phosphorylated on serine residues 106 and 293 both in insect and in mammalian cells. These sites can also be efficiently phosphorylated by the cdc2 and MAP kinases in vitro. Mutation of these residues does not affect the capacity of the Tax protein to function as a transactivator. Indeed, the Tax proteins mutated at one or both serines increase LTR-directed viral transcription at levels similar to those obtained with wild-type Tax in cell culture. Moreover, inhibition of Tax phosphorylation by W7, a calmodulin antagonist, does not alter its transactivation activity. Thus, phosphorylation on serines 106 and 293 is not required for transactivation by Tax. However, simultaneous substitution of both serines into alanine residues destroys the capacity of Tax to cooperate with the Ha-ras oncogene to transform primary rat embryo fibroblasts and induce tumors in nude mice. When the serines were replaced with aspartic acid residues, the oncogenic potential of Tax was maintained indicating that the negative charge rather than the phosphate group itself was required for Tax oncogenicity. Finally, to assess the role of the serine residues in vivo, recombinant viruses which express the Tax mutants were constructed and injected into sheep. It appeared that the mutated proviruses replicate at levels similar to the wild-type virus in vivo. We conclude that Tax phosphorylation is dispensable for transactivation and viral replication in vivo but is required for its oncogenic potential in vitro.
نوع الوثيقة: article in journal/newspaper
اللغة: English
تدمد: 0950-9232
1476-5594
العلاقة: urn:issn:0950-9232; urn:issn:1476-5594; https://orbi.uliege.be/handle/2268/32476Test; info:hdl:2268/32476; https://orbi.uliege.be/bitstream/2268/32476/1/Willems%20et%20al%201998.pdfTest; scopus-id:2-s2.0-7144253147; info:pmid:9619825
DOI: 10.1038/sj.onc.1201765
الإتاحة: https://doi.org/10.1038/sj.onc.1201765Test
https://orbi.uliege.be/handle/2268/32476Test
https://orbi.uliege.be/bitstream/2268/32476/1/Willems%20et%20al%201998.pdfTest
حقوق: open access ; http://purl.org/coar/access_right/c_abf2Test ; info:eu-repo/semantics/openAccess
رقم الانضمام: edsbas.C4DCA683
قاعدة البيانات: BASE
الوصف
تدمد:09509232
14765594
DOI:10.1038/sj.onc.1201765