Journal article
Interaction of HTLV-1 Tax protein with calreticulin: Implications for Tax nuclear export and secretion
Biomedicine & pharmacotherapy, v 61(4)
2007
PMID: 17395420
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Human T cell leukemia virus type 1 (HTLV-1) is the etiologic agent of adult T cell leukemia (ATL) and HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). The HTLV-1 transcriptional transactivator protein Tax plays an integral role in virus replication and disease progression. Traditionally, Tax is described as a nuclear protein where it performs its primary role as a transcriptional transactivator. However, recent studies have clearly shown that Tax can also be localized to the cytoplasm where it has been shown to interact with a number of host transcription factors most notably NF-κB, constitutive expression of which is directly related to the T cell transforming properties of Tax in ATL patients. The presence of a functional nuclear export signal (NES) within Tax and the secretion of full-length Tax have also been demonstrated previously. Additionally, release of Tax from HTLV-1-infected cells and the presence of cell-free Tax was demonstrated in the CSF of HAM/TSP patients suggesting that the progression to HAM/TSP might be mediated by the ability of Tax to function as an extracellular cytokine. Therefore, in both ATL and HAM/TSP Tax nuclear export and nucleocytoplasmic shuttling may play a critical role, the mechanism of which remains unknown. In this study, we have demonstrated that the calcium binding protein calreticulin interacts with Tax by co-immunoprecipitation. This interaction was found to localize to a region at or near the nuclear membrane. In addition, differential expression of calreticulin was demonstrated in various cell types that correlated with their ability to retain cytoplasmic Tax, particularly in astrocytes. Finally, a comparison of a number of HTLV-1-infected T cell lines to non-infected T cells revealed higher expression of calreticulin in infected cells implicating a direct role for this protein in HTLV-1 infection.
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Details
- Title
- Interaction of HTLV-1 Tax protein with calreticulin: Implications for Tax nuclear export and secretion
- Creators
- Timothy Alefantis - Vital Probes, Inc., 1300 Old Plank Road, Mayfield, PA 18433, USAKatherine E Flaig - Department of Microbiology and Immunology, and Center for Molecular Virology and Neuroimmunology, Center for Cancer Biology, Institute of Molecular Medicine and Infectious Disease, Drexel University College of Medicine, Philadelphia, PA 19102, USABrian Wigdahl - Department of Microbiology and Immunology, and Center for Molecular Virology and Neuroimmunology, Center for Cancer Biology, Institute of Molecular Medicine and Infectious Disease, Drexel University College of Medicine, Philadelphia, PA 19102, USAPooja Jain - Department of Microbiology and Immunology, and Center for Molecular Virology and Neuroimmunology, Center for Cancer Biology, Institute of Molecular Medicine and Infectious Disease, Drexel University College of Medicine, Philadelphia, PA 19102, USA
- Publication Details
- Biomedicine & pharmacotherapy, v 61(4)
- Publisher
- Elsevier SAS
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Microbiology and Immunology
- Web of Science ID
- WOS:000247134300002
- Scopus ID
- 2-s2.0-34248226475
- Other Identifier
- 991014877752904721
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- Web of Science research areas
- Medicine, Research & Experimental
- Pharmacology & Pharmacy