Human T-Cell Leukemia Virus Type 2 Tax Mutants That Selectively Abrogate NFκB or CREB/ATF Activation Fail To Transform Primary Human T Cells
| Autor: | Patrick L. Green, Murli Narayan, Alex C. Minella, Zhi-Yu Fang, Ted M. Ross |
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| Rok vydání: | 2000 |
| Předmět: |
Transcriptional Activation
T-Lymphocytes viruses Immunology Activating transcription factor Virus Replication CREB Microbiology Transformation and Oncogenesis ATF/CREB Transactivation Proviruses Virology Tumor Cells Cultured Humans Cyclic AMP Response Element-Binding Protein Transcription factor Cells Cultured Activating Transcription Factor 2 biology Human T-lymphotropic virus 2 NF-kappa B Transcription Factor RelA Gene Products tax Cell Transformation Viral NFKB1 Activating transcription factor 2 Phenotype Mutagenesis Insect Science biology.protein Cancer research Signal transduction Transcription Factors |
| Zdroj: | Journal of Virology. 74:2655-2662 |
| ISSN: | 1098-5514 0022-538X |
| DOI: | 10.1128/jvi.74.6.2655-2662.2000 |
| Popis: | Human T-cell leukemia virus (HTLV) Tax protein has been implicated in the HTLV oncogenic process, primarily due to its pleiotropic effects on cellular genes involved in growth regulation and cell cycle control. To date, several approaches attempting to correlate Tax activation of the CREB/activating transcription factor (ATF) or NFκB/Rel transcriptional activation pathway to cellular transformation have yielded conflicting results. In this study, we use a unique HTLV-2 provirus (HTLV c-enh ) that replicates by a Tax-independent mechanism to directly assess the role of Tax transactivation in HTLV-mediated T-lymphocyte transformation. A panel of well-characterized tax-2 mutations is utilized to correlate the respective roles of the CREB/ATF or NFκB/Rel signaling pathway. Our results demonstrate that viruses expressing tax-2 mutations that selectively abrogate NFκB/Rel or CREB/ATF activation display distinct phenotypes but ultimately fail to transform primary human T lymphocytes. One conclusion consistent with our results is that the activation of NFκB/Rel provides a critical proliferative signal early in the cellular transformation process, whereas CREB/ATF activation is required to promote the fully transformed state. However, complete understanding will require correlation of Tax domains important in cellular transformation to those Tax domains important in the modulation of gene transcription, cell cycle control, induction of DNA damage, and other undefined activities. |
| Databáze: | OpenAIRE |
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