Differences in the Ability of Human T-Cell Lymphotropic Virus Type 1 (HTLV-1) and HTLV-2 Tax To Inhibit p53 Function
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- Renaud Mahieux
- <!--label omitted: 1-->Laboratory of Receptor Biology and Gene Expression,1
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- Cynthia A. Pise-Masison
- <!--label omitted: 1-->Laboratory of Receptor Biology and Gene Expression,1
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- Paul F. Lambert
- <!--label omitted: 1-->Laboratory of Receptor Biology and Gene Expression,1
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- Christophe Nicot
- <!--label omitted: 2-->Basic Research Laboratory, Section of Animal Models and Retroviral Infection,2 and
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- Laura De Marchis
- <!--label omitted: 3-->Laboratory of Tumor Immunology and Biology,3National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892;
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- Antoine Gessain
- <!--label omitted: 4-->Unité d'Oncologie Virale, Institut Pasteur, 75724 Paris, France4;
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- Patrick Green
- <!--label omitted: 5-->Departments of Veterinary Biosciences and Molecular Virology, Immunology, and Medical Genetics, Center for Retrovirus Research and Comprehensive Cancer Center, The Ohio State University, Columbus, Ohio 43210-10935; and
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- William Hall
- <!--label omitted: 6-->Department of Microbiology, University College, Dublin, Ireland6
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- John N. Brady
- <!--label omitted: 1-->Laboratory of Receptor Biology and Gene Expression,1
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<jats:title>ABSTRACT</jats:title> <jats:p>We have analyzed the functional activity of the p53 tumor suppressor in human T-cell lymphotropic virus type 2 (HTLV-2)-transformed cells. Abundant levels of the p53 protein were detected in both HTLV-2A and -2B virus-infected cell lines. The p53 was functionally inactive, however, both in transient-transfection assays using a p53 reporter plasmid and in induction of p53-responsive genes in response to gamma irradiation. We further investigated HTLV-2A Tax and HTLV-2B Tax effects on p53 activity. Interestingly, although Tax-2A and -2B inactivate p53, the Tax-2A protein appears to inhibit p53 function less efficiently than either Tax-1 or Tax-2B. In transient-cotransfection assays, Tax-1 and Tax-2B inactivated p53 by 80%, while Tax2A reduced p53 activity by 20%. In addition, Tax-2A does not increase the steady-state level of cellular p53 as well as Tax-1 or -2B does in the same assays. Cotransfection assays demonstrated that Tax-2A could efficiently transactivate CREB-responsive promoters to the same level as Tax-1 and Tax-2B, indicating that the protein was functional. This report provides evidence of the first functional difference between the HTLV-2A and -2B subtypes. This comparison of the action of HTLV-1 and HTLV-2 Tax proteins on p53 function will provide important insights into the mechanism of HTLV transformation.</jats:p>
収録刊行物
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- Journal of Virology
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Journal of Virology 74 (15), 6866-6874, 2000-08
American Society for Microbiology
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詳細情報 詳細情報について
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- CRID
- 1361981468538875904
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- NII論文ID
- 30020794847
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- NII書誌ID
- AA00708779
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- ISSN
- 10985514
- 0022538X
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