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Characterization of a nuclear export signal within the human T cell leukemia virus type I transactivator protein Tax
Journal article   Open access   Peer reviewed

Characterization of a nuclear export signal within the human T cell leukemia virus type I transactivator protein Tax

Timothy Alefantis, Kate Barmak, Edward W Harhaj, Christian Grant and Brian Wigdahl
The Journal of biological chemistry, v 278(24), pp 21814-21822
13 Jun 2003
DOI: https://doi.org/10.1074/jbc.M211576200
PMID: 12670929
Featured in Collection :   UN Sustainable Development Goals @ Drexel
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https://doi.org/10.1074/jbc.M211576200View
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Abstract

Green Fluorescent Proteins Humans Transcriptional Activation Molecular Sequence Data Cytoplasm - metabolism NF-kappa B - metabolism Recombinant Fusion Proteins - metabolism Cell Nucleus - metabolism Transfection Gene Products, tax - metabolism Active Transport, Cell Nucleus Dimerization Protein Structure, Tertiary Amino Acid Sequence Cell Line Leucine - metabolism Mutagenesis, Site-Directed Jurkat Cells Fatty Acids, Unsaturated - pharmacology Plasmids - metabolism Blotting, Western Models, Biological HeLa Cells Mutation Microscopy, Fluorescence Luminescent Proteins - metabolism
Human T cell leukemia virus type I (HTLV-I) is the etiologic agent of adult T cell leukemia and HTLV-I-associated myelopathy/tropical spastic paraparesis. The HTLV-I transactivator protein Tax plays an integral role in the etiology of adult T cell leukemia, as expression of Tax in T lymphocytes has been shown to result in immortalization. In addition, Tax is known to interface with numerous transcription factor families, including activating transcription factor/cAMP response element-binding protein and nuclear factor-kappaB, requiring Tax to localize to both the nucleus and cytoplasm. In this report, the nucleocytoplasmic localization of Tax was examined in Jurkat, HeLa, and U-87 MG cells. The results reported herein indicate that Tax contains a leucine-rich nuclear export signal (NES) that, when fused to green fluorescent protein (GFP), can direct nuclear export via the CRM-1 pathway, as determined by leptomycin B inhibition of nuclear export. However, cytoplasmic localization of full-length Tax was not altered by treatment with leptomycin B, suggesting that native Tax utilizes another nuclear export pathway. Additional support for the presence of a functional NES has also been shown because the NES mutant Tax(L200A)-GFP localized to the nuclear membrane in the majority of U-87 MG cells. Evidence has also been provided suggesting that the Tax NES likely exists as a conditionally masked signal because the truncation mutant TaxDelta214-GFP localized constitutively to the cytoplasm. These results suggest that Tax localization may be directed by specific changes in Tax conformation or by specific interactions with cellular proteins leading to changes in the availability of the Tax NES and nuclear localization signal.

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Web of Science research areas
Biochemistry & Molecular Biology
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