HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

J. Biol. Chem., Vol. 280, Issue 17, 17353-17362, April 29, 2005

This Article Full Text Full Text (PDF) All Versions of this Article: 280/17/17353    most recent M409851200v1 Submit a Letter to Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Alefantis, T. Articles by Wigdahl, B. Search for Related Content PubMed PubMed Citation Articles by Alefantis, T. Articles by Wigdahl, B. Social Bookmarking                      What's this?

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||

From the Department of Microbiology and Immunology, Pennsylvania State University, College of Medicine, Hershey, Pennsylvania 17033, the ^¶Department of Microbiology and Immunology, University of Miami School of Medicine, Miami, Florida 33136, and the Department of Microbiology and Immunology, Institute for Molecular Medicine and Infectious Disease, Drexel University College of Medicine, Philadelphia, Pennsylvania 19129

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- 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.

Received for publication, August 26, 2004 , and in revised form, January 14, 2005.

^* These studies were supported by United States Public Health Service/National Institutes of Health Grant CA54559 (to B. W.) and by Ruth L. Kirschstein National Research Service Award 1 F31 NS 044801 (to K. M.). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

^|| To whom correspondence should be addressed: Dept. of Microbiology and Immunology, Drexel University College of Medicine, 2900 Queen Ln., Philadelphia, PA 19129. Tel.: 215-991-8352; Fax: 215-848-2271; E-mail: brian.wigdahl{at}drexelmed.edu.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				S. C. Y. Ku, J. Lee, J. Lau, M. Gurumurthy, R. Ng, S. H. Lwa, J. Lee, Z. Klase, F. Kashanchi, and S.-H. Chao XBP-1, a Novel Human T-Lymphotropic Virus Type 1 (HTLV-1) Tax Binding Protein, Activates HTLV-1 Basal and Tax-Activated Transcription J. Virol., May 1, 2008; 82(9): 4343 - 4353. [Abstract] [Full Text] [PDF]

				P. Jain, K. Mostoller, K. E. Flaig, J. Ahuja, V. Lepoutre, T. Alefantis, Z. K. Khan, and B. Wigdahl Identification of Human T Cell Leukemia Virus Type 1 Tax Amino Acid Signals and Cellular Factors Involved in Secretion of the Viral Oncoprotein J. Biol. Chem., November 23, 2007; 282(47): 34581 - 34593. [Abstract] [Full Text] [PDF]

				P. Jain, J. Ahuja, Z. K. Khan, S. Shimizu, O. Meucci, S. R. Jennings, and B. Wigdahl Modulation of dendritic cell maturation and function by the Tax protein of human T cell leukemia virus type 1 J. Leukoc. Biol., July 1, 2007; 82(1): 44 - 56. [Abstract] [Full Text] [PDF]

				T. Tsuji, N. Sheehy, V. W. Gautier, H. Hayakawa, H. Sawa, and W. W. Hall The Nuclear Import of the Human T Lymphotropic Virus Type I (HTLV-1) Tax Protein Is Carrier- and Energy-independent J. Biol. Chem., May 4, 2007; 282(18): 13875 - 13883. [Abstract] [Full Text] [PDF]

				N. S. Harhaj, S.-C. Sun, and E. W. Harhaj Activation of NF-{kappa}B by the Human T Cell Leukemia Virus Type I Tax Oncoprotein Is Associated with Ubiquitin-dependent Relocalization of I{kappa}B Kinase J. Biol. Chem., February 9, 2007; 282(6): 4185 - 4192. [Abstract] [Full Text] [PDF]

				C. Grant, P. Jain, M. Nonnemacher, K. E. Flaig, B. Irish, J. Ahuja, A. Alexaki, T. Alefantis, and B. Wigdahl AP-1-directed human T cell leukemia virus type 1 viral gene expression during monocytic differentiation J. Leukoc. Biol., September 1, 2006; 80(3): 640 - 650. [Abstract] [Full Text] [PDF]

				M. Moriuchi and H. Moriuchi Induction of Lactoferrin Gene Expression in Myeloid or Mammary Gland Cells by Human T-Cell Leukemia Virus Type 1 (HTLV-1) Tax: Implications for Milk-Borne Transmission of HTLV-1 J. Virol., July 15, 2006; 80(14): 7118 - 7126. [Abstract] [Full Text] [PDF]

				S. Ozden, V. Mouly, M.-C. Prevost, A. Gessain, G. Butler-Browne, and P.-E. Ceccaldi Muscle Wasting Induced by HTLV-1 Tax-1 Protein: An in Vitro and in Vivo Study Am. J. Pathol., December 1, 2005; 167(6): 1609 - 1619. [Abstract] [Full Text] [PDF]