Human T-cell leukemia virus type 2 Tax mutants that selectively abrogate NFκB or CREB/ATF activation fail to transform primary human T cells

被引:50
作者
Ross, TM
Narayan, M
Fang, ZY
Minella, AC
Green, PL
机构
[1] Ohio State Univ, Dept Vet Biosci, Columbus, OH 43210 USA
[2] Vanderbilt Univ, Sch Med, Dept Microbiol & Immunol, Nashville, TN 37232 USA
[3] Ohio State Univ, Dept Mol Virol Immunol & Med Genet, Columbus, OH 43210 USA
[4] Ohio State Univ, Ctr Retrovirus Res, Columbus, OH 43210 USA
[5] Ohio State Univ, Ctr Comprehens Canc, Columbus, OH 43210 USA
关键词
D O I
10.1128/JVI.74.6.2655-2662.2000
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
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 NF kappa B/Rel transcriptional activation pathway to cellular transformation have yielded conflicting results. In this study, we use a unique HTLV-2 provirus (HTLVc-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 NF kappa B/Rel signaling pathway. Our results demonstrate that viruses expressing tax-2 mutations that selectively abrogate NF kappa B/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 NF kappa B/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.
引用
收藏
页码:2655 / 2662
页数:8
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