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Identification of human T cell leukemia virus type 1 tax amino acid signals and cellular factors involved in secretion of the viral oncoprotein
Journal article   Open access   Peer reviewed

Identification of human T cell leukemia virus type 1 tax amino acid signals and cellular factors involved in secretion of the viral oncoprotein

Pooja Jain, Kate Mostoller, Katherine E Flaig, Jaya Ahuja, Veronique Lepoutre, Timothy Alefantis, Zafar K Khan and Brian Wigdahl
The Journal of biological chemistry, v 282(47), pp 34581-34593
23 Nov 2007
DOI: https://doi.org/10.1074/jbc.M707317200
PMID: 17897946
Featured in Collection :   UN Sustainable Development Goals @ Drexel
url
https://doi.org/10.1074/jbc.M707317200View
Published, Version of Record (VoR) Open

Abstract

Cricetinae Gene Products, tax - cerebrospinal fluid Jurkat Cells Leukemia-Lymphoma, Adult T-Cell - genetics Humans Gene Silencing Paraparesis, Tropical Spastic - cerebrospinal fluid Leukemia-Lymphoma, Adult T-Cell - cerebrospinal fluid Protein Transport - physiology Gene Products, tax - genetics Leukemia-Lymphoma, Adult T-Cell - virology Animals Gene Products, tax - metabolism Paraparesis, Tropical Spastic - genetics Human T-lymphotropic virus 1 - metabolism Human T-lymphotropic virus 1 - pathogenicity Paraparesis, Tropical Spastic - virology Human T-lymphotropic virus 1 - genetics Nuclear Export Signals - physiology Protein Structure, Tertiary - physiology
Human T cell leukemia virus type 1 (HTLV-1) is the etiologic agent of a number of pathologic abnormalities, including adult T cell leukemia (ATL) and HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). The viral oncoprotein Tax has been implicated in the pathogenesis of these diseases. Recently, cell-free Tax was detected in the cerebrospinal fluid of HAM/TSP patients, implying that extracellular Tax may be relevant to neurologic disease. Additionally, the presence of a nuclear export signal within Tax and its active secretion has been demonstrated in vitro. However, the mechanism of Tax secretion remains to be established. Studies reported herein elucidate the process of Tax secretion and identify domains of Tax critical to its subcellular localization and secretion. Tax was shown to interact with a number of cellular secretory pathway proteins in both the model cell line BHK (baby hamster kidney)-21 and an HTLV-1-infected T cell line, C8166, physiologically relevant to HTLV-1-induced disease. Silencing of selected components of the secretory pathway affected Tax secretion, further confirming regulated secretion of Tax. Additionally, mutations in two putative secretory signals within Tax DHE and YTNI resulted in aberrant subcellular localization of Tax and significantly altered protein secretion. Together, these studies demonstrate that Tax secretion is a regulated event facilitated by its interactions with proteins of the cellular secretory pathway and the presence of secretory signals within the carboxyl-terminal domain of the protein.

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