Logo image
Back
Secretion of the human T cell leukemia virus type I transactivator protein tax
Journal article   Open access   Peer reviewed

Secretion of the human T cell leukemia virus type I transactivator protein tax

Timothy Alefantis, Kate Mostoller, Pooja Jain, Edward Harhaj, Christian Grant and Brian Wigdahl
The Journal of biological chemistry, v 280(17), pp 17353-17362
29 Apr 2005
DOI: https://doi.org/10.1074/jbc.M409851200
PMID: 15659397
Featured in Collection :   UN Sustainable Development Goals @ Drexel
url
https://doi.org/10.1074/jbc.M409851200View
Published, Version of Record (VoR) Open

Abstract

Tetradecanoylphorbol Acetate - pharmacology Humans Transcriptional Activation Endoplasmic Reticulum - metabolism Brefeldin A - pharmacology Cytoplasm - metabolism Central Nervous System - embryology Necrosis Transfection Gene Products, tax - metabolism Time Factors Culture Media Transcription, Genetic Neurons - metabolism Cell Culture Techniques Interleukin-6 - metabolism Protein Structure, Tertiary Cell Line Green Fluorescent Proteins - metabolism Cricetinae Enzyme-Linked Immunosorbent Assay Neurodegenerative Diseases - metabolism Plasmids - metabolism Animals Models, Biological Cell Line, Tumor Ionomycin - pharmacology Bacterial Proteins - metabolism Golgi Apparatus - metabolism DNA, Complementary - metabolism Apoptosis 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 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.

Metrics

5 Record Views
52 citations in Web of Science
57 citations in Scopus

Details

UN Sustainable Development Goals (SDGs)

This publication has contributed to the advancement of the following goals:

#3 Good Health and Well-Being

InCites Highlights

Data related to this publication, from InCites Benchmarking & Analytics tool:

Collaboration types
Domestic collaboration
Web of Science research areas
Biochemistry & Molecular Biology
Logo image