Disease relevance of STLV1gp4

• The Tax protein of human T-lymphotropic virus (HTLV)-1 activates expression of the HTLV-1 long terminal repeat through a DNA element that resembles the cellular cyclic AMP-regulated enhancer (CRE) [1].
• In a cotransfection assay, the Tax protein of both HTLV-I and HTLV-II specifically activated transcription from the IL-1alpha promoter in an uninfected Jurkat cell line [2].
• The human T-cell leukemia virus type 1 Tax protein transforms human T lymphocytes, which can lead to the development of adult T-cell leukemia [3].
• The human T-cell leukemia virus (HTLV-I)-encoded Tax protein is a potent transcriptional activator that stimulates expression of the integrated provirus [4].
• Transcriptional activation of JC virus by human T-lymphotropic virus type I Tax protein in human neuronal cell lines [5].

High impact information on STLV1gp4

• We also show that the fraction of Tax protein that localizes to centrosomes interacts with TAX1BP2, a novel centrosomal protein composed almost entirely of coiled-coil domains [6].
• Our purpose was to determine whether the mechanism by which Tax protein induces transformation in HTLV- or BLV-infected cells involves DNA damage [7].
• The Tax protein of HTLV-1 induces these same kappa B-specific proteins, but in contrast to immune stimulation, HTLV-1 infection of T cells leads to constitutive IL-2R alpha gene expression and immortalization [8].
• These observations indicate that Tax protein binds to CREB and CRE modulator and the complexes then bind to the 21-bp enhancer, suggesting that the complex binding to the enhancer mediates trans-activation of transcription [9].
• Although Tax protein is the main target of cytotoxic T lymphocyte (CTL) on human T-cell lymphotropic virus type I (HTLV-I)-infected cells, and Tax peptide 11 through 19 binding to HLA-A*02 has been shown to elicit a strong CTL response, there are patients with adult T-cell leukemia (ATL) bearing HLA-A*02 [10].

Chemical compound and disease context of STLV1gp4

• Here we report biological properties of phosphoramidate oligonucleotides targeted against the human T cell leukemia virus type-I Tax protein, the major transcriptional transactivator of this human retrovirus [11].
• The HTLV-I-mediated effect does not require productive infection: exposure to heat-inactivated HTLV-I virions, purified Tax protein, or HTLV-I Env glycoprotein also induced expression of HIV-1 [12].
• We recently reported a novel multivalent cytotoxic T-lymphocyte peptide construct derived from the Tax protein of HTLV-1 separated by arginine spacers that elicited high cellular responses against individual epitopes simultaneously in human leukocyte antigen (HLA)-A*0201 transgenic mice [13].

Biological context of STLV1gp4

• Transactivation of the human interleukin-6 gene by human T-lymphotropic virus type 1 Tax protein [14].
• Both tax mRNA expression and Tax protein synthesis were inhibited significantly, resulting in inhibition of synovial cell growth and induction of apoptosis [15].
• Transcriptional up-regulation of the c-sis/platelet-derived growth factor-B (PDGF-B) proto-oncogene by the Tax protein of human T-cell leukemia virus type 1 has been implicated as one possible mechanism of cellular transformation by human T-cell leukemia virus type 1 [16].
• The Tax protein of the human T-cell leukemia virus type I (HTLV-1) deregulates cell growth and alters the role of IL-2 in infected cells [17].
• The Tax protein of HTLV-I, a positive transcriptional activator of HTLV-I gene expression, is a viral oncogene that also increases transcription of cellular genes including GM-CSF, IL-2R alpha and IL-2 [18].

Anatomical context of STLV1gp4

• The cells phenotypically resemble HTLV-immortalized lymphocytes and contain episomally persisting recombinant rhadinoviral sequences, which stably express functional Tax protein [19].
• When introduced into tax-transformed fibroblasts ex vivo, only the uniformly modified anti-tax phosphoramidate oligodeoxynucleotide caused a sequence-dependent reduction in the Tax protein level [11].
• Imbalanced expression of glutamate-glutamine cycle enzymes induced by human T-cell lymphotropic virus type 1 Tax protein in cultivated astrocytes [20].
• The expressed Tax protein is localized in the nucleus and associated with the yeast nuclear matrix fraction [21].

Associations of STLV1gp4 with chemical compounds

• Transactivation was >7-fold in Jurkat cells stably expressing the Tax protein (Jurkat-Tax) than in Jurkat E6.1 cells and was further enhanced in Jurkat-Tax cells stimulated with 12-O-tetradecanoylphorbol-13-acetate and the calcium ionophore, ionomycin [22].
• 3'-Terminal phosphorothioate-modified antisense ODNs were shown to efficiently inhibit Tax protein expression both in vitro and in vivo [23].
• Metabolism in astrocytes altered by Tax protein may lead to deleterious effects if it modifies the extracellular levels of glutamine, glutamate, and GABA and thus modulates neuronal excitability and osmotic equilibrium in the central nervous system of HTLV-1-infected patients [20].
• Presentation of a new H-2D(k)-restricted epitope in the Tax protein of human T-lymphotropic virus type I is enhanced by the proteasome inhibitor lactacystin [24].
• Owing to its multipotent activities, the HTLV-I-encoded Tax protein was suspected to inhibit ceramide synthesis [25].

Analytical, diagnostic and therapeutic context of STLV1gp4

• To investigate the diagnostic implications of virion-associated Tax protein, sera from HTLV-I-infected individuals were compared on HUT-102 and MT-2 virus Western blots [26].
• We also performed histopathological examination as well as immunohistochemistry of HTLV-I-derived Tax protein in eight synovial tissues taken from carrier patients [27].

References