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Interaction of HTLV-1 Tax protein with calreticulin: Implications for Tax nuclear export and secretion
Journal article   Open access   Peer reviewed

Interaction of HTLV-1 Tax protein with calreticulin: Implications for Tax nuclear export and secretion

Timothy Alefantis, Katherine E Flaig, Brian Wigdahl and Pooja Jain
Biomedicine & pharmacotherapy, v 61(4)
2007
PMID: 17395420
url
https://doi.org/10.1016/j.biopha.2007.02.005View
Published, Version of Record (VoR) Open

Abstract

HTLV-1 Tax Calreticulin Nucleocytoplasmic shuttling
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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Web of Science research areas
Medicine, Research & Experimental
Pharmacology & Pharmacy
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