Document Detail


Secretion of the human T cell leukemia virus type I transactivator protein tax.
MedLine Citation:
PMID:  15659397     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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 protein Tax is well known as a transcriptional transactivator and inducer of cellular transformation. However, it is also known that extracellular Tax induces the production and release of cytokines, such as tumor necrosis factor-alpha and interleukin-6, which have adverse effects on cells of the central nervous system. The cellular process by which Tax exits the cell into the extracellular environment is currently unknown. In most cell types, Tax has been shown to localize primarily to the nucleus. However, Tax has also been found to accumulate in the cytoplasm. The results contained herein begin to characterize the process of Tax secretion from the cell. Specifically, cytoplasmic Tax was demonstrated to localize to organelles associated with the cellular secretory process including the endoplasmic reticulum and Golgi complex. Additionally, it was demonstrated that full-length Tax was secreted from both baby hamster kidney cells and a human kidney tumor cell line, suggesting that Tax enters the secretory pathway in a leaderless manner. Tax secretion was partially inhibited by brefeldin A, suggesting that Tax migrated from the endoplasmic reticulum to the Golgi complex. In addition, combined treatment of Tax-transfected BHK-21 cells with phorbol myristate acetate and ionomycin resulted in a small increase in the amount of Tax secreted, suggesting that a fraction of cytoplasmic Tax was present in the regulated secretory pathway. These studies begin to provide a link between Tax localization to the cytoplasm, the detection of Tax in the extracellular environment, its possible role as an extracellular effector molecule, and a potential role in neurodegenerative disease associated with HTLV-I infection.
Authors:
Timothy Alefantis; Kate Mostoller; Pooja Jain; Edward Harhaj; Christian Grant; Brian Wigdahl
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, U.S. Gov't, P.H.S.     Date:  2005-01-19
Journal Detail:
Title:  The Journal of biological chemistry     Volume:  280     ISSN:  0021-9258     ISO Abbreviation:  J. Biol. Chem.     Publication Date:  2005 Apr 
Date Detail:
Created Date:  2005-04-25     Completed Date:  2005-06-21     Revised Date:  2008-11-21    
Medline Journal Info:
Nlm Unique ID:  2985121R     Medline TA:  J Biol Chem     Country:  United States    
Other Details:
Languages:  eng     Pagination:  17353-62     Citation Subset:  IM    
Affiliation:
Department of Microbiology and Immunology, Pennsylvania State University, College of Medicine, Hershey, Pennsylvania 17033, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Apoptosis
Bacterial Proteins / metabolism
Brefeldin A / pharmacology
Cell Culture Techniques
Cell Line
Cell Line, Tumor
Central Nervous System / embryology
Cricetinae
Culture Media
Cytoplasm / metabolism
DNA, Complementary / metabolism
Endoplasmic Reticulum / metabolism
Enzyme-Linked Immunosorbent Assay
Gene Products, tax / metabolism*
Golgi Apparatus / metabolism
Green Fluorescent Proteins / metabolism
Humans
Interleukin-6 / metabolism
Ionomycin / pharmacology
Luminescent Proteins / metabolism
Models, Biological
Necrosis
Neurodegenerative Diseases / metabolism
Neurons / metabolism
Plasmids / metabolism
Protein Structure, Tertiary
Tetradecanoylphorbol Acetate / pharmacology
Time Factors
Transcription, Genetic
Transcriptional Activation
Transfection
Grant Support
ID/Acronym/Agency:
1 F31 NS 044801/NS/NINDS NIH HHS; CA54559/CA/NCI NIH HHS
Chemical
Reg. No./Substance:
0/Bacterial Proteins; 0/Culture Media; 0/Cyan Fluorescent Protein; 0/DNA, Complementary; 0/Gene Products, tax; 0/Interleukin-6; 0/Luminescent Proteins; 0/yellow fluorescent protein, Bacteria; 147336-22-9/Green Fluorescent Proteins; 16561-29-8/Tetradecanoylphorbol Acetate; 20350-15-6/Brefeldin A; 56092-81-0/Ionomycin

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