Biomedical subjects

Yuetsu Tanaka

Publications and source records attributed to Yuetsu Tanaka.

At least 37 records · Page 2Linked to original sources

PubMed2005

A new sensitive and quantitative HTLV-I-mediated cell fusion assay in T cells.

Similar to several other viruses, human T cell leukemia virus type I (HTLV-I) induces the formation of multinucleated giant cells (also known as syncytium) when amplified in tissue culture. These syncytia result from the fusion of infected cells with uninfected cells. Due to the intrinsic difficulty of infecting cells with cell-free HTLV-I virions, syncytium formation has become an important tool in the study of HTLV-I infection and transmission. Since most HTLV-I-based cell fusion assays rely on the use of non-T cells, the aim of this study was to optimize a new HTLV-I-induced cell fusion assay in which HTLV-I-infected T cell lines are co-cultured with T cells that have been transfected with an HTLV-I long terminal repeat (LTR) luciferase reporter construct. We demonstrate that co-culture of various HTLV-I-infected T cells with different transfected T cell lines resulted in induction of luciferase activity. Cell-to-cell contact and expression of the viral gp46 envelope protein was crucial for this induction while other cell surface proteins (including HSC70) did not have a significant effect. This quantitative assay was shown to be very sensitive. In this assay, the cell fusion-mediated activation of NF-kappaB and the HTLV-I LTR occurred through previously described Tax-dependent signaling pathways. This assay also showed that cell fusion could activate Tax-inducible cellular promoters. These results thus demonstrate that this new quantitative HTLV-I-dependent cell fusion assay is versatile, highly sensitive, and can provide an important tool to investigate cellular promoter activation and intrinsic signaling cascades that modulate cellular gene expression.

CD4-Positive T-Lymphocytes↗

PubMed2005

PDZ domain-binding motif of human T-cell leukemia virus type 1 Tax oncoprotein is essential for the interleukin 2 independent growth induction of a T-cell line.

BACKGROUND: Human T-cell leukemia virus type 1 (HTLV-1) is the etiologic agent of adult T-cell leukemia (ATL), whereas HTLV type 2 (HTLV-2), is not associated with ATL or any other leukemia. HTLV-1 encodes the transforming gene tax1, whose expression in an interleukin (IL)-2-dependent T-cell line (CTLL-2) induces IL-2-independent growth. RESULTS: In this study, we demonstrated that IL-2-independent growth induction by Tax1 was abrogated by mutations of the PDZ domain-binding motif (PBM) at the Tax1 C-terminus. HTLV-2 Tax2, which shares 75% amino acid identity with Tax1 but does not have a PBM, was not able to induce IL-2-independent growth of CTLL-2. CONCLUSION: Our results suggest that Tax1, through interaction with PDZ domain protein(s) induces IL-2-independent growth, which may be a factor in multi-step leukemogenesis caused by HTLV-1.

Binding Sites↗

PubMed2005

Transcriptional activation of survivin through the NF-kappaB pathway by human T-cell leukemia virus type I tax.

Survivin, a unique member of the inhibitor of apoptosis protein family, is overexpressed in many cancers and considered to play an important role in oncogenesis. We previously reported the survivin expression profile in ATL, a CD4-positive T-cell malignancy caused by HTLV-I. HTLV-I Tax is thought to play an important role in immortalization of T cells. We have shown also that the expression of Tax protected the mouse T-cell line CTLL-2 against apoptosis induced by deprivation of IL-2 and converted its growth from being IL-2 dependent to being IL-2 independent through the NF-kappaB pathway. In our study, we demonstrate that constitutive expression of survivin was associated with resistance to apoptosis after IL-2 deprivation in Tax-expressing CTLL-2 cells. Transient transfection assays showed that survivin promoter was transactivated by Tax, via the activation of NF-kappaB. Pharmacological NF-kappaB inhibition resulted in suppression of survivin expression and caused apoptosis of Tax-expressing CTLL-2 cells. Our findings suggest that activated NF-kappaB signaling contributes directly to malignant progression of ATL by preventing apoptosis, acting through the prosurvival protein survivin.

Animals↗

PubMed2005

Human T-lymphotropic virus, type 1, tax protein triggers microtubule reorientation in the virological synapse.

We showed recently that the human T-lymphotropic virus, type 1 (HTLV-1), spreads directly from cell to cell via a virological synapse. The HTLV-1 virological synapse resembles the immunological synapse; each is a specialized contact between a lymphocyte and another cell that contains organized protein microdomains, and each involves repolarization of the T-cell microtubule cytoskeleton. However, formation of the virological synapse is not triggered by T-cell receptor-mediated antigen recognition. On the basis of our previous data, we postulated that formation of the viral synapse was triggered by a conjunction of two signals, one from HTLV-1 infection of the T-cell and one from cell-cell contact. We have recently identified ICAM-1 engagement as a cell-contact signal that causes the microtubule polarization associated with the virological synapse. Here we used confocal microscopy of T-lymphocytes naturally infected with HTLV-1 or transfected with individual HTLV-1 genes to investigate the role of the viral transcriptional transactivator protein Tax. Polarization of the microtubules was induced by cell-cell contact or by cross-linking T-cell surface molecules with monoclonal antibodies adsorbed to latex beads. We show that Tax, which is mainly found in the nucleus, is also present at two specific extranuclear sites as follows: around the microtubule organizing center in association with the cis-Golgi and in the cell-cell contact region. We show that expression of Tax provides an intracellular signal that synergizes with ICAM-1 engagement to cause the T-cell microtubule polarization observed at the virological synapse.

Actin Cytoskeleton↗

PubMed2005

APOBEC3G targets human T-cell leukemia virus type 1.

BACKGROUND: Apolipoprotein B mRNA-editing enzyme-catalytic polypeptide-like 3G (APOBEC3G) is a host cellular protein with a broad antiviral activity. It inhibits infectivitiy of a wide variety of retroviruses by deaminating deoxycytidine (dC) into deoxyuridine (dU) in newly synthesized minus strand DNA, resulting in G-to-A hypermutation of the viral plus strand DNA. To clarify the mechanism of its function, we have examined the antiviral activity of APOBEC3G on human T-cell leukemia virus type 1 (HTLV-1), the first identified human retrovirus. RESULTS: In this study, we have demonstrated that overexpressed as well as endogenous APOBEC3G were incorporated into HTLV-1 virions and that APOBEC3G inhibited the infection of HTLV-1. Interestingly, several inactive mutants of APOBEC3G also inhibited HTLV-1 and no G-to-A hypermutation was induced by APOBEC3G in HTLV-1 genome. Furthermore, we introduced the human immunodeficiency virus type 1 (HIV-1) vif gene into HTLV-1 producing cell line, MT-2, to antagonize APOBEC3G by reducing its intracellular expression and virion incorporation, which resulted in upregulation of the infectivity of produced viruses. CONCLUSION: APOBEC3G is incorporated into HTLV-1 virions and inhibits the infection of HTLV-1 without exerting its cytidine deaminase activity. These results suggest that APOBEC3G might act on HTLV-1 through different mechanisms from that on HIV-1 and contribute to the unique features of HTLV-1 infection and transmission.

APOBEC-3G Deaminase↗

PubMed2005

Engagement of specific T-cell surface molecules regulates cytoskeletal polarization in HTLV-1-infected lymphocytes.

Cell-cell contact is required for efficient transmission of human T-lymphotropic virus type 1 (HTLV-1). An HTLV-1-infected cell polarizes its microtubule-organizing center (MTOC) toward the cell-cell junction; HTLV-1 core (Gag) complexes and the HTLV-1 genome accumulate at the point of contact and are then transferred to the uninfected cell. However, the mechanisms involved in this cytoskeletal polarization and transport of HTLV-1 complexes are unknown. Here, we tested the hypothesis that engagement of a specific T-cell surface ligand is synergistic with HTLV-1 infection in causing polarization of the MTOC to the cell contact region. We show that antibodies to intercellular adhesion molecule-1 (ICAM-1; CD54) caused MTOC polarization at a higher frequency in HTLV-1-infected cells. ICAM-1 is upregulated on HTLV-1-infected cells, and, in turn, ICAM-1 on the cell surface upregulates HTLV-1 gene expression. We propose that a positive feedback loop involving ICAM-1 and HTLV-1 Tax protein facilitates the formation of the virologic synapse and contributes to the T-cell tropism of HTLV-1. In contrast, MTOC polarization induced in T cells by antibodies to CD3 or CD28 was significantly inhibited by HTLV-1 infection.

CD4-Positive T-Lymphocytes↗

PubMed2005

Potential immunogenicity of adult T cell leukemia cells in vivo.

Experimental vaccines targeting human T cell leukemia virus type-I (HTLV-I) Tax have been demonstrated in a rat model of HTLV-I-induced lymphomas. However, the scarcity of HTLV-I-expression and the presence of defective HTLV-I-proviruses in adult T cell leukemia (ATL) cells have raised controversy about the therapeutic potential of HTLV-I-targeted immunotherapy in humans. We investigated the expression of HTLV-I antigens in fresh ATL cells by using both in vitro and in vivo assays. In flow cytometric analysis, we found that 3 of 5 acute-type and six of fifteen chronic-type ATL patients tested showed significant induction of HTLV-I Tax and Gag in their ATL cells in a 1-day culture. Concomitantly with HTLV-I-expression, these ATL cells expressed co-stimulatory molecules such as CD80, CD86 and OX40, and showed elevated levels of antigenicity against allogeneic T cells and HTLV-I Tax-specific cytotoxic T-lymphocytes (CTL). Representative CTL epitopes restricted by HLA-A2 or A24 were conserved in 4 of 5 acute-type ATL patients tested. Furthermore, spleen T cells from rats, which had been subcutaneously inoculated with formalin-fixed uncultured ATL cells, exhibited a strong interferon gamma-producing helper T cell responses specific for HTLV-I Tax-expressing cells. Our study indicated that ATL cells from about half the patients tested readily express HTLV-I antigens including Tax in vitro, and that ATL cells express sufficient amounts of Tax or Tax-induced antigens to evoke specific T cell responses in vivo.

Adult↗

PubMed2005

Interaction of HTLV-1 Tax and methyl-CpG-binding domain 2 positively regulates the gene expression from the hypermethylated LTR.

Epigenetic regulation of gene expression is critical in the maintenance of cellular homeostasis. Dysregulation of normal epigenetic transcription occurs in abnormal physiological conditions, such as those seen in cancer cells and cells infected with parasites, making the mechanism underlying abnormal epigenetic transcription of great interest. Gene expression of human T-cell leukemia virus type 1 (HTLV-1) is regulated by a viral transcriptional stimulator, Tax. We herein report a novel mechanism of transcription from the HTLV-1 long terminal repeat (LTR) that is regulated by Tax. In this study, we determined that Tax is able to activate transcription from the LTR, even when it was heavily methylated. In addition, the methyl-CpG-binding domain 2 (MBD2) protein played an important role in Tax-mediated transcriptional activation. We demonstrated the importance of a physical interaction between Tax and MBD2 in enhancing the transcriptional activity of Tax against the methylated LTR. Furthermore, we identified the formation of a protein complex composed of MBD2 and Tax bound to the methylated LTR. We propose a new model of epigenetic regulation by MBD2 acting in concert with a virally encoded transactivator, Tax. Our observation provides insight into the epigenetic regulation of gene expression and the diverse mechanisms of transcriptional regulation using methylated promoters.

Binding Sites↗

PubMed2005

NK cell regulation of T cell-mediated responses.

NK cells promote adaptive immune responses through their production of type 1 and type 2 cytokines or chemokines. Secretion of these factors by activated NK cells influences the differentiation of B and T lymphocytes. Increasing evidence indicates that NK cells are also directly involved in dendritic cell (DC) maturation. By contrast, a potential role for direct cell-cell interactions between NK and T lymphocytes, in particular CD4(+) T cells, has not been explored. We provide evidence that activated human NK cells are able of promoting TcR-dependent proliferation of resting autologous peripheral blood CD4(+) T cells by a process that involves costimulatory molecules of the immunoglobulin (Ig) and tumor necrosis factor (TNF) superfamilies. These findings suggest a novel link between natural and adaptative immune responses.

Cell Communication↗

PubMed2005

Identification of HIV-1 epitopes that induce the synthesis of a R5 HIV-1 suppression factor by human CD4+ T cells isolated from HIV-1 immunized hu-PBL SCID mice.

We have previously reported that immunization of the severe combined immunodeficiency (SCID) mice reconstituted with human peripheral blood mononuclear cells (PBMC) (hu-PBL-SCID mice) with inactivated human immunodeficiency virus type-1 (HIV-1)-pulsed-autologous dendritic cells (HIV-DC) elicits HIV-1-reactive CD4(+) T cells that produce an as yet to be defined novel soluble factor in vitro with anti-viral properties against CCR5 tropic (R5) HIV-1 infection. These findings led us to perform studies designed to identify the lineage of the cell that synthesizes such a factor in vivo and define the epitopes of HIV-1 protein that have specificity for the induction of such anti-viral factor. Results of our studies show that this property is a function of CD4(+) but not CD8(+) T cells. Human CD4(+) T cells were thus recovered from the HIV-DC-immunized hu-PBL-SCID mice and were re-stimulated in vitro by co-culture for 2 days with autologous adherent PBMC as antigen presenting cells, APC previously pulsed with inactivated HIV in IL-2-containing medium to expand HIV-1-reactive CD4(+) T cells. Aliquots of these re-stimulated CD4(+) T cells were then co-cultured with similar APC's that were previously pulsed with 10 microg/ml of a panel of HIV peptides for an additional 2 days, and their culture supernatants were examined for the production of both the R5 HIV-1 suppression factor and IFN-gamma. The data presented herein show that the HIV-1 primed CD4(+) T cells produced the R5 suppression factor in response to a wide variety of HIV-1 gag, env, pol, nef or vif peptides, depending on the donor of the CD4(+) T cells. Simultaneous production of human interferon (IFN)-gamma was observed in some cases. These results indicate that human CD4(+) T cells in PBMC of HIV-1 naive donors have a wide variety of HIV-1 epitope-specific CD4(+) T cell precursors that are capable of producing the R5 HIV-1 suppression factor upon DC-based vaccination with whole inactivated HIV-1.

Animals↗

PubMed2005

A functional CD8+ cell assay reveals individual variation in CD8+ cell antiviral efficacy and explains differences in human T-lymphotropic virus type 1 proviral load.

The CD8+ lymphocyte response is a main component of host immunity, yet it is difficult to quantify its contribution to the control of persistent viruses. Consequently, it remains controversial as to whether CD8+ cells have a biologically significant impact on viral burden and disease progression in infections such as human immunodeficiency virus-1 and human T-lymphotropic virus type I (HTLV-I). Experiments to ascertain the impact of CD8+ cells on viral burden based on CD8+ cell frequency or specificity alone give inconsistent results. Here, an alternative approach was developed that directly quantifies the impact of CD8+ lymphocytes on HTLV-I proviral burden by measuring the rate at which HTLV-I-infected CD4+ cells were cleared by autologous CD8+ cells ex vivo. It was demonstrated that CD8+ cells reduced the lifespan of infected CD4+ cells to 1 day, considerably shorter than the 30 day lifespan of uninfected cells in vivo. Furthermore, it was shown that HTLV-I-infected individuals vary considerably in the rate at which their CD8+ cells clear infected cells, and that this was a significant predictor of their HTLV-I proviral load. Forty to 50 % of between-individual variation in HTLV-I proviral load was explained by variation in the rate at which CD8+ cells cleared infected cells. This novel approach demonstrates that CD8+ cells are a major determinant of HTLV-I proviral load. This assay is applicable to quantifying the CD8+ cell response to other viruses and malignancies and may be of particular importance in assessing vaccines.

Adult↗

PubMed2005

Human leukocyte antigen-class II-negative long-term cultured human T-cell leukemia virus type-I-infected T-cell lines with progressed cytological properties significantly induce superantigen-dependent normal T-cell proliferation.

While most human T-cell leukemia virus type-I (HTLV-I)-infected T cells express abundant class II antigens, some aggressive-type adult T-cell leukemia (ATL) cells lose their expression. To investigate the significance of the class II antigen of HTLV-I infected cells, the progressiveness of HTLV-I-infected long-term cultured T-cell lines was evaluated, and then their antigen-presenting capacity was examined using a superantigen, staphylococcus enterotoxin B (SEB). Among the cell lines derived from peripheral blood, HPB-ATL-T (ATL-T), HPB-ATL-2 (ATL-2) and HPB-ATL-O were more progressed than Tax exclusively expressing HPB-CTL-I (CTL-I), because the former deleted p16 gene (polymerase chain reaction (PCR)) and strongly transcribed survivin (reverse transcriptase-PCR). Notably, interferon gamma-independent loss of class II expression of ATL-T and ATL-2 was found. In antigen-presenting experiments, however, both cell lines induced SEB-dependent significant T-cell proliferation estimated by [(3)H] thymidine uptake. No class II-re-expressed ATL-2 cells were observed in the SEB-presenting cultures by indirect immunofluorescence, and only minimum inhibition of SEB-dependent T-cell response by anti-human leukocyte antigen (HLA)-DR monoclonal antibody was observed. These findings suggest that both ATL-T and ATL-2 very effectively present SEB to T cells less dependently on class II molecules. These less immunogenic leukemic cells of aggressive ATL may contribute to disease aggression.

Adult↗

PubMed2005

Aberrant activation of the interleukin-2 autocrine loop through the nuclear factor of activated T cells by nonleukemogenic human T-cell leukemia virus type 2 but not by leukemogenic type 1 virus.

Human T-cell leukemia virus type 1 (HTLV-1) but not HTLV-2 is associated with adult T-cell leukemia. We found that HTLV-2 Tax2 protein stimulated reporter gene expression regulated by the interleukin (IL)-2 promoter through the nuclear factor of activated T cells (NFAT) in a human T-cell line (Jurkat). However, the activity of HTLV-1 Tax1 was minimal in this system. T-cell lines immortalized by HTLV-2 but not HTLV-1 constitutively exhibited activated NFAT in the nucleus and constitutively expressed IL-2 mRNA. Cyclosporine A, an inhibitor of NFAT activation, abrogated the induction of IL-2 mRNA in HTLV-2-immortalized T-cell lines and concomitantly inhibited cell growth. This growth inhibition was rescued by the addition of IL-2 to the culture. Furthermore, anti-IL-2 receptor antibodies significantly reduced the proliferation of HTLV-2-infected T-cell lines but not that of HTLV-1-infected cells. Our results suggest that Tax2 activates an IL-2 autocrine loop mediated through NFAT that supports the growth of HTLV-2-infected cells under low-IL-2 conditions. This mechanism would be especially important in vivo, where this autocrine mechanism establishes a nonleukemogenic life-long HTLV-2 infection. The results also suggest that differences in long-term cytokine production between HTLV-1 and HTLV-2 infection are another factor for the differences in pathogenesis.

Base Sequence↗

PubMed2005

Fucoidan extracted from Cladosiphon okamuranus Tokida induces apoptosis of human T-cell leukemia virus type 1-infected T-cell lines and primary adult T-cell leukemia cells.

Adult T-cell leukemia (ATL) is caused by human T-cell leukemia virus type 1 (HTLV-1) and remains incurable. The highest endemic area of HTLV-1 carriers in Japan is located in Okinawa, and novel treatments are urgently needed in this area. We extracted fucoidan, a sulfated polysaccharide, from the brown seaweed Cladosiphon okamuranus Tokida cultivated in Okinawa, Japan and examined its tumor-suppression activity against ATL. Fucoidan significantly inhibited the growth of peripheral blood mononuclear cells of ATL patients and HTLV-1-infected T-cell lines but not that of normal peripheral blood mononuclear cells. Fucoidan induced apoptosis of HTLV-1-infected T-cell lines mediated through downregulation of cellular inhibitor of apoptosis protein-2 and survivin and G1 phase accumulation through the downregulation of cyclin D2, c-myc, and hyperphosphorylated form of the retinoblastoma tumor suppressor protein. Further analysis showed that fucoidan inactivated NF-kappaB and activator protein-1 and inhibited NF-kappaB-inducible chemokine, C-C chemokine ligand 5 (regulated on activation, normal T expressed and secreted) production, and homotypic cell-cell adhesion of HTLV-1-infected T-cell lines. In vivo use of fucoidan resulted in partial inhibition of growth of tumors of an HTLV-1-infected T-cell line transplanted subcutaneously in severe combined immune deficient mice. Our results indicate that fucoidan is a potentially useful therapeutic agent for patients with ATL.

Animals↗

PubMed2004

Cross-talk between activated human NK cells and CD4+ T cells via OX40-OX40 ligand interactions.

It is important to understand which molecules are relevant for linking innate and adaptive immune cells. In this study, we show that OX40 ligand is selectively induced on IL-2, IL-12, or IL-15-activated human NK cells following stimulation through NKG2D, the low affinity receptor for IgG (CD16) or killer cell Ig-like receptor 2DS2. CD16-activated NK cells costimulate TCR-induced proliferation, and IFN-gamma produced by autologous CD4+ T cells and this process is dependent upon expression of OX40 ligand and B7 by the activated NK cells. These findings suggest a novel and unexpected link between the natural and specific immune responses, providing direct evidence for cross-talk between human CD4+ T cells and NK receptor-activated NK cells.

Antigens, CD↗

PubMed2004

Genetic and epigenetic inactivation of tax gene in adult T-cell leukemia cells.

To clarify the status of tax gene, we analyzed human T-cell leukemia virus type-I (HTLV-I) associated cell lines and fresh adult T-cell leukemia (ATL) cells. We compared 2 types of HTLV-I associated cell lines: one was derived from leukemic cells (leukemic cell line) and the other from nonleukemic cells (nonleukemic cell line). Although all nonleukemic cell lines expressed Tax, it could not be detected in 3 of 5 leukemic cell lines, in which nonsense mutation or deletion (60 bp) of tax genes, and DNA methylation in 5'-LTR were identified as the responsible changes. We found such genetic changes of the tax gene in 5 of 47 fresh ATL cases (11%). The tax gene transcripts could be detected in 14 of 41 fresh ATL cases (34%) by RT-PCR. In ATL cases with genetic changes that could not produce Tax protein, the tax gene was frequently transcribed, suggesting that such cells do not need the transcriptional silencing. Although DNA methylation of 5'-LTR was detected in the fresh ATL cases (19 of 28 cases; 68%), the complete methylation associated with transcriptional silencing was observed only in 4 cases. Since partial methylation could not silence the transcription, and the tax gene transcription was not detected in 27 of 41 cases (66%), the epigenetic change(s) other than DNA methylation is considered to play an important role in the silencing.

Acetylation↗

PubMed2004

A CCR2-V64I polymorphism affects stability of CCR2A isoform.

OBJECTIVE: A valine to isoleucine substitution at position 64 of CCR2 (CCR2-64I) is associated with a delay in progression to AIDS in HIV-1-infected individuals. The aim of the present study is to elucidate the molecular mechanism underlying the effect of this allele. DESIGN: We analysed the effect of the 64I substitution on levels of expression of CCR2A and CCR2B, two CCR2 isoforms produced by alternative splicing. METHODS: Sendai virus vector was used to express CCR2 molecules. RESULTS: While CCR2B trafficked well to the cell surface, CCR2A, which differs from CCR2B only by the sequence of its C-terminal cytoplasmic tail, was detected predominantly in the cytoplasm. The level of expression of CCR2A-64I was significantly higher than that of CCR2A without the substitution. On the other hand, the 64I substitution did not affect levels of CCR2B expression. Pulse-chase experiments revealed that the 64I substitution increased the half-life of CCR2A in cells. When co-expressed with CCR5, CCR2A-64I interfered more severely with cell surface expression of CCR5 than did wild-type CCR2A. Furthermore, immunoprecipitation experiments showed that CCR2A co-precipitated with an immature form of CCR5. CONCLUSION: These results suggest that CCR2A binds to CCR5 in the cytoplasm and down-modulates its surface expression. We propose that the increased ability of CCR2A-64I to down-modulate CCR5 expression might be a possible cause of a delay in HIV-1 disease progression in patients with this allele.

Amino Acid Sequence↗

PubMed2004

Human T-cell leukemia virus type 1 Tax oncoprotein induces and interacts with a multi-PDZ domain protein, MAGI-3.

Human T-cell leukemia virus type 1 (HTLV-1) is the causative agent of adult T-cell leukemia (ATL), whereas the closely related virus HTLV-2 has not been associated with such malignant conditions. HTLV-1 Tax1 oncoprotein transforms a rat fibroblast cell line (Rat-1) much more efficiently than does HTLV-2 Tax2. By using a differential display analysis, we isolated MAGI-3 as a Tax1-inducible gene in Rat-1 cells. Reverse transcription-polymerase chain reaction (RT-PCR) analysis confirmed that Tax1 induced MAGI-3 in Rat-1 cells. MAGI-3 has multiple PDZ domains and interacted with Tax1 but not Tax2 in 293T cells. The interaction of Tax1 with MAGI-3 was dependent on a PDZ domain-binding motif, which is missing in Tax2. The interaction of Tax1 with MAGI-3 altered their respective subcellular localization, and moreover, the interaction correlated well with the high transforming activities of Tax1 in Rat-1 cells relative to Tax2. MAGI-3 mRNA and the allied MAGI-1, but not MAGI-2, were expressed in HTLV-1-infected T-cell lines. Our results suggest that the interaction of Tax1 and MAGI-3 alters their respective biological activities, which may play a role in transformation by Tax1 as well as in the pathogenesis of HTLV-1-associated diseases.

Amino Acid Motifs↗