Biomedical subjects

Masahiro Fujii

Publications and source records attributed to Masahiro Fujii.

At least 19 recordsLinked to original sources

PubMed2006

A novel KRAB-Zinc finger protein interacts with latency-associated nuclear antigen of Kaposi's sarcoma-associated herpesvirus and activates transcription via terminal repeat sequences.

Kaposi's sarcoma-associated herpesvirus (KSHV) establishes latent infection in various cells in vitro as well as KSHV-associated tumor cells in vivo. The latency-associated nuclear antigen (LANA) of KSHV is one of a small number of genes expressed in the latent phase of KSHV infection. This antigen is crucial for establishment of the latent infection, such as replication of KSHV genomic DNA and maintenance of infection via direct interaction with terminal repeats (TRs) in the viral genome. Using a yeast two-hybrid screening method, we isolated a novel LANA-interacting protein (designated as KZLP; KRAB Zinc finger LANA interacting Protein) from a human peripheral leukocyte cDNA library. KZLP encodes a KRAB domain and 12 Kruppel-type zinc fingers. Reverse transcription polymerase chain reaction showed that KZLP was expressed ubiquitously in various cell lines including those infected with KSHV. A luciferase assay showed that KZLP could activate the KSHV open reading frame K1 promoter containing TRs in 293T cells, and that such activation required multiple TR sequences. In contrast, LANA repressed the activity of the K1 promoter through TRs, and again this repression required multiple TR units. Moreover, LANA almost completely abrogated the KZLP-mediated transcriptional activation. Our results suggest that KZLP and LANA regulate gene expression through TRs in the KSHV viral genome, including the K1 gene in latent KSHV-infected cells.

Antigens, Viral↗

PubMed2006

Human T-cell leukemia virus type 2 Tax protein induces interleukin 2-independent growth in a T-cell line.

BACKGROUND: While human T-cell leukemia virus type 1 (HTLV-1) is a causative agent of adult T-cell leukemia, HTLV type 2 (HTLV-2) is not associated with this malignancy. Accumulating evidence suggests that Tax, a transforming protein of HTLV-1 or HTLV-2, plays a crucial role in the distinctive pathogenesis of these two infections. We herein examined whether Tax2 by itself has a growth promoting activity in a mouse T-cell line CTLL-2, and compared the activity with that of Tax1. RESULTS: We found that Tax2 converts the cell growth of CTLL-2 from an interleukin(IL)-2-dependent growth into an independent one. Cyclosporine A, an inhibitor of transcription factor NFAT, inhibited the growth of two out of four Tax2-transformed CTLL-2 cells, but it had little effect on two Tax1-transformed cells. While the HTLV-2-transformed human T-cell lines produce a significant amount of IL-2, Tax2-transformed CTLL-2 cells only produced a minimal amount of IL-2. These results thus suggest that NFAT-inducible gene(s) other than IL-2 play a role in the cell growth of Tax2-transformed CTLL-2 cells. CONCLUSION: These results show that HTLV-2 Tax2 by itself has a growth promoting activity toward a T-cell line CTLL-2, and the CTLL-2 assay used in this study may therefore be a useful tool for comparing the activity of Tax2 with that of Tax1 in T-cells, thereby elucidating the mechanism of HTLV-1 specific leukemogenesis.

Animals↗

PubMed2006

Inactivation of tumor suppressor Dlg1 augments transformation of a T-cell line induced by human T-cell leukemia virus type 1 Tax protein.

BACKGROUND: The interaction of human T-cell leukemia virus type 1 (HTLV-1) Tax1 protein with the tumor suppressor Dlg1 is correlated with cellular transformation. RESULTS: Here, we show that Dlg1 knockdown by RNA interference increases the ability of Tax1 to transform a mouse T-cell line (CTLL-2), as measured interleukin (IL)-2-independent growth. A Tax1 mutant defective for the Dlg1 interaction showed reduced transformation of CTLL-2 compared to wild type Tax1, but the transformation was minimally affected by Dlg1 reduction. The few Tax1DeltaC-transduced CTLL-2 cells that became transformed expressed less Dlg1 than parental cells, suggesting that Dlg1-low cells were selectively transformed by Tax1DeltaC. Moreover, all human T-cell lines immortalized by HTLV-1, including the recombinant HTLV-1-containing Tax1DeltaC, expressed less Dlg1 than control T-cell lines. CONCLUSION: These results suggest that inactivation of Dlg1 augments Tax1-mediated transformation of CTLL-2, and PDZ protein(s) other than Dlg1 are critically involved in the transformation.

Animals↗

PubMed2006

Involvement of HTLV-I Tax and CREB in aneuploidy: a bioinformatics approach.

BACKGROUND: Adult T-cell leukemia (ATL) is a complex and multifaceted disease associated with human T-cell leukemia virus type 1 (HTLV-I) infection. Tax, the viral oncoprotein, is considered a major contributor to cell cycle deregulation in HTLV-I transformed cells by either directly disrupting cellular factors (protein-protein interactions) or altering their transcription profile. Tax transactivates these cellular promoters by interacting with transcription factors such as CREB/ATF, NF-kappaB, and SRF. Therefore by examining which factors upregulate a particular set of promoters we may begin to understand how Tax orchestrates leukemia development. RESULTS: We observed that CTLL cells stably expressing wild-type Tax (CTLL/WT) exhibited aneuploidy as compared to a Tax clone deficient for CREB transactivation (CTLL/703). To better understand the contribution of Tax transactivation through the CREB/ATF pathway to the aneuploid phenotype, we performed microarray analysis comparing CTLL/WT to CTLL/703 cells. Promoter analysis of altered genes revealed that a subset of these genes contain CREB/ATF consensus sequences. While these genes had diverse functions, smaller subsets of genes were found to be involved in G2/M phase regulation, in particular kinetochore assembly. Furthermore, we confirmed the presence of CREB, Tax and RNA Polymerase II at the p97Vcp and Sgt1 promoters in vivo through chromatin immunoprecipitation in CTLL/WT cells. CONCLUSION: These results indicate that the development of aneuploidy in Tax-expressing cells may occur in response to an alteration in the transcription profile, in addition to direct protein interactions.

Aneuploidy↗

PubMed2006

Rupture of a normal-sized, non-dissected distal aortic arch in a Marfan patient.

We successfully repaired a rupture of a normal-sized, non-dissected distal aortic arch in a patient with Marfan syndrome. Six years previously she had undergone repair of the thoraco-abdominal aortic aneurysm with a 24-mm knitted Dacron graft for type B chronic aortic dissection. The rupture site was located at the back of the native distal aortic arch just 10 mm above the proximal anastomosis, and just below the left subclavian artery. This unexpected situation might be related to dilatation of the knitted Dacron graft up to 34 mm (142%), thus stretching out the fragile native aorta in this Marfan patient.

Adult↗

PubMed2005

A novel, selective, and orally available antagonist for CC chemokine receptor 3.

CC chemokine ligand 11 (CCL11/eotaxin) and other CC chemokine receptor 3 (CCR3) ligands (CCL24/eotaxin-2, CCL26/eotaxin-3, CCL13/monocyte chemotactic protein-4, etc.) play important roles in the chemotaxis and activation of eosinophils and other CCR3-expressing cells (basophils, mast cells, and CD4(+) T helper 2 cells) in allergic inflammation incidents, including asthma and rhinitis. A newly synthesized compound, N-{(3R)-1-[(6-fluoro-2-naphthyl)methyl]pyrrolidin-3-yl}-2-{1-[(5-hydroxy-3-methylpyridin-2-yl)carbonyl]piperidin-4-ylidene}-acetamide hemifumarate (YM-355179), inhibited the binding of CCL11 and CCL5/regulated on activation normal T cell expressed and secreted to CCR3-expressing B300-19 cells with IC(50) values of 7.6 and 24 nM, respectively. In contrast, YM-355179 did not affect the binding of CCL5 to CCR1 or CCR5. In functional assays, YM-355179 inhibited CCL11-induced, intracellular Ca(2+) influx, chemotaxis, and eosinophil degranulation with IC(50) values of 8.0, 24, and 29 nM, respectively. YM-355179 did not, however, affect any CC chemokine receptor (CCR1, CCR2, CCR4, or CCR5)-mediated Ca(2+) influx signals. Furthermore, oral administration of YM-355179 (1 mg/kg) inhibited CCL11-induced shape change of whole blood eosinophils in cynomolgus monkeys. Intravenous injection of YM-355179 (1 mg/kg) also inhibited eosinophil infiltration into airways of cynomolgus monkeys after segmental bronchoprovocation with CCL11. These results indicate that YM-355179 is a novel, selective, and orally available CCR3 antagonist with therapeutic potential for treating eosinophil-related allergic inflammatory diseases.

Administration, Oral↗

PubMed2005

Myocardial protection with intermittent cross-clamp fibrillation: does preconditioning play a role?

OBJECTIVE: Previously, we showed intermittent cross-clamp fibrillation afforded equivalent protection to cardioplegia. This study examined whether protection induced by intermittent cross-clamp fibrillation involves an ischemic preconditioning mechanism. METHODS: Isolated Langendorff-perfused rat hearts were subjected to three different studies to determine: Study 1, whether a single intermittent cross-clamp fibrillation episode (10 min) and reperfusion (10 min) before prolonged ischemia acts as a preconditioning trigger for protection; Study 2, whether cardioprotection induced by intermittent cross-clamp fibrillation alone (no prolonged ischemia) involves a preconditioning mechanism; Study 3, whether intermittent cross-clamp fibrillation cardioprotection can be prevented by targeting putative components of the preconditioning mechanism (protein kinase C or the mitochondrial ATP-sensitive potassium (K(ATP)) channel). Hearts were reperfused (60 min) and recovery of function (left ventricular developed pressure measured using an intraventricular balloon) and myocardial injury (creatine kinase leakage) were measured. RESULTS: In Study 1, recovery of function in the single intermittent cross-clamp fibrillation hearts was 61+/-3% (mean+/-SEM) (p<0.05) compared to 41+/-2% in control group; glibenclamide (a non-specific ATP-sensitive potassium (K(ATP))-channel blocker) prevented this preconditioning protection (37+/-4%). In Study 2, recovery of function in intermittent cross-clamp fibrillation hearts (62+/-3%) was significantly (p<0.05) higher than intermittent cross-clamp fibrillation hearts treated with glibenclamide (33+/-2%) and ischemia hearts (30+/-5%). In Study 3, protection by intermittent cross-clamp fibrillation (60+/-3%; p<0.05) was attenuated by protein kinase C inhibition (chelerythrine, 34+/-3%) and mitochondrial K(ATP)-channel blockade (5-hydroxydecanoate, 27+/-4%) to levels not significantly different from that of ischemia hearts (25+/-4%). CONCLUSIONS: The cardioprotective efficacy of intermittent cross-clamp fibrillation was attenuated by protein kinase C inhibition or K(ATP)-channel blockade. Involvement of these putative preconditioning cascade components in association with cardioprotection induced by intermittent cross-clamp fibrillation, suggests a role for the ischemic preconditioning mechanism.

Animals↗

PubMed2005

12th International Conference on Human Retrovirology: HTLV and Related Retroviruses.

The 12th International Conference on Human Retrovirology: HTLV and Related Retroviruses, was held at the Half Moon Hotel in Montego Bay, Jamaica, from June 22nd to June 25th 2005. The scientific conference, sponsored by the International Retrovirology Association, is held biennially at rotating international venues around the world. The meeting brings together basic scientists, epidemiologists and clinical researchers to discuss findings to prevent HTLV infection or develop new therapies against HTLV-mediated diseases. The Association fosters the education and training of young scientists to bring new approaches to the complex problems of HTLV research, such as translational research to bring findings from the laboratory into clinical trials that benefit HTLV-infected patients. The breadth and quality of research presentations and workshops at the 12th International Conference indicate that these goals are being accomplished. As HTLV research enters its third decade a new generation of scientists face many challenges. However, HTLV scientists and clinicians displayed exciting new approaches and discoveries during plenary talks and poster sessions. The conference encouraged research in HTLV infections and disease, fostered collaborations, and stimulated new partnerships between clinicians and scientists to encourage clinical trials and novel therapeutic interventions.

Animals↗

PubMed2005

B-type natriuretic peptide as an integrated risk marker in non-ST elevation acute coronary syndromes.

BACKGROUND: Elevated B-type natriuretic peptide (BNP) levels show prognostic significance in patients with non-ST elevation acute coronary syndromes, but the underlying pathophysiology remains unclear. METHODS: Two hundred and eighteen consecutive patients with non-ST elevation acute coronary syndromes were studied retrospectively. We compared clinical characteristics between groups with plasma BNP levels above or below the median value, and performed multiple logistic regression analysis to identify independent predictors of supramedian BNP levels. RESULTS: Patients with supramedian BNP (>or=134 pg/ml) were more likely to be elderly (>or=75 years) with diabetes, prior myocardial infarction, and a history of coronary artery bypass grafting. They also had higher cardiac marker levels, a higher Killip class, a lower left ventricular ejection fraction, renal insufficiency (creatinine>or=1.5 mg/dl), and more 3-vessel disease. In multivariate analysis, the strongest independent predictor of supramedian BNP levels was 3-vessel disease (chi(2)=12.1), followed by old age (chi(2)=10.3), renal insufficiency (chi(2)=5.0), higher Killip class (chi(2)=4.2), and lower left ventricular ejection fraction (chi(2)=4.1). All 11 patients dying in hospital had supramedian BNP levels. Its elevation reflected the risk of 3-vessel disease and coronary artery bypass grafting regardless of troponin status. CONCLUSION: In unselected patients with non-ST elevation acute coronary syndromes, an increase of BNP is correlated with the extent of myocardial ischemia, age, renal insufficiency, and ventricular dysfunction. It may be a useful biomarker integrating conventional risk factors for risk stratification in this population.

Aged↗

PubMed2005

Deregulation of cell-signaling pathways in HTLV-1 infection.

Human T-lymphotropic virus type 1 (HTLV-1) infection is associated with the clonal expansion and transformation of mature T lymphocytes. While the mechanisms involved are incompletely understood the viral regulatory protein Tax plays a central role in these processes. Recent studies employing genomic and proteomic approaches have demonstrated the marked complexity of gene deregulation associated with Tax expression and confirmed the remarkable pleiotropism of this protein as evidenced by the numerous Tax-cellular protein interactions in infected cells. In this review, we summarize the role of Tax in the deregulation of selected cellular-signaling pathways. Specifically, this has focused on the influence and interaction of Tax with the AP-1 and NF-AT transcription factors, PDZ domain-containing proteins, Rho-GTPases, and the Janus kinase/signal transducer and activator of transcription and transforming growth factor-beta-signaling pathways. In addition to identifying the deregulation of events within these pathways, attempts have been made to highlight differences between HTLV-1 and -2, which may relate to differences in their pathogenic properties.

Gene Expression Regulation, Viral↗

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

Elevated expression of CD30 in adult T-cell leukemia cell lines: possible role in constitutive NF-kappaB activation.

BACKGROUND: Human T-cell leukemia virus type 1 (HTLV-1) is associated with the development of adult T-cell leukemia (ATL). HTLV-1 encoded Tax1 oncoprotein activates the transcription of genes involved in cell growth and anti-apoptosis through the NF-kappaB pathway, and is thought to play a critical role in the pathogenesis of ATL. While Tax1 expression is usually lost or minimal in ATL cells, these cells still show high constitutive NF-kappaB activity, indicating that genetic or epigenetic changes in ATL cells induce activation independent of Tax1. The aim of this study was to identify the molecules responsible for the constitutive activation of NF-kappaB in ATL cells using a retroviral functional cloning strategy. RESULTS: Using enhanced green fluorescent protein (EGFP) expression and blasticidin-resistance as selection markers, several retroviral cDNA clones exhibiting constitutive NF-kappaB activity in Rat-1 cells, including full-length CD30, were obtained from an ATL cell line. Exogenous stable expression of CD30 in Rat-1 cells constitutively activated NF-kappaB. Elevated expression of CD30 was identified in all ATL lines examined, and primary ATL cells from a small number of patients (8 out of 66 cases). CONCLUSION: Elevated CD30 expression is considered one of the causes of constitutive NF-kappaB activation in ATL cells, and may be involved in ATL development.

Animals↗

PubMed2005

Studies of non-nucleoside HIV-1 reverse transcriptase inhibitors. Part 2: synthesis and structure-activity relationships of 2-cyano and 2-hydroxy thiazolidenebenzenesulfonamide derivatives.

In a previous study, we described the structure-activity relationships (SARs) for a series of thiazolidenebenzenesulfonamide derivatives. These compounds were found to be highly potent inhibitors of the wild type (WT) and Y181C mutant reverse transcriptases (RTs) and modest inhibitors of K103N RT. These molecules are thus considered to be a novel class of non-nucleoside HIV-1 RT inhibitors (NNRTIs). In this paper, we have examined the effects of substituents on both the thiazolidene and benzenesulfonamide moieties. Introduction of a 2-cyanophenyl ring into these moieties significantly enhanced anti-HIV-1 activity, whereas a 2-hydroxyphenyl group endowed potent activity against RTs, including K103N and Y181C mutants. Among the series of molecules examined, 10l and 18b (YM-228855), combinations of 2-cyanophenyl and 4-methyl-5-isopropylthiazole moieties, showed extremely potent anti-HIV-1 activity. The EC50 values of 101 and 18b were 0.0017 and 0.0018 microM, respectively. These values were lower than that of efavirenz (3). Compound 11g (YM-215389), a combination of 2-hydroxyphenyl and 4-chloro-5-isopropylthiazole moieties, proved to be the most active against both K103N and Y181C RTs with IC50 values of 0.043 and 0.013 microM, respectively.

Cell Line↗

PubMed2005

Nucleotide sequences and functions of the Epstein-Barr virus latent membrane protein 1 genes isolated from salivary gland lymphoepithelial carcinomas.

Epstein-Barr virus (EBV) infection is associated with salivary gland lymphoepithelial carcinoma (SLEC) and nasopharyngeal carcinoma (NPC). EBV is a ubiquitous herpes virus world wide, but EBV-associated SLEC and NPC are prevalent in restricted regions such as south areas of China, Southeastern Asia and Greenland (Eskimos). To examine whether particular EBV variants play roles in the development of SLEC and NPC, we isolated the complete EBV LMP1 genes from 12 paraffin-embedded biopsy samples of SLECs isolated from China, Taiwan and Russia, and compared these LMP1 genes with those of NPC (CAO) and the prototype B95-8 EBV. Nucleotide sequence analysis showed that SLECs LMP1 is more similar to that of CAO than that of prototype B95-8. The analysis also identified several conserved (67-100%) variations in SLEC-LMP1 and CAO-LMP1 distinct from B95-8-LMP1. These included 10-amino acid deletion, 5-amino acid deletion and 12-single amino acid variations. A SLEC-LMP1 gene with the aforementioned conserved variations inhibited the growth of an embryonic kidney cell line (293T), highly activated the NF-kappaB pathway, and these activities were equivalent to those of B95-8 and CAO. These findings suggest that the biological functions of SLEC-LMP 1 are similar to those of B95-8-LMP1 and CAO-LMP1, and that these amino acid variations including the well-known 10-aa deletion did not affect these two prominent activities. While the present results could not uncover functional differences between SLEC-LMP1 and B95-8-LMP1, the nucleotide sequences and the molecular clone of LMP1 directly isolated from SLEC patients will be a useful tool to identify the high-pathogenic EBV strain(s), associated with SLEC and NPC.

Amino Acid Sequence↗

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↗

PubMed2004

Studies of nonnucleoside HIV-1 reverse transcriptase inhibitors. Part 1: Design and synthesis of thiazolidenebenzenesulfonamides.

A random high-throughput screening (HTS) program to discover novel nonnucleoside reverse transcriptase inhibitors (NNRTIs) has been carried out with MT-4 cells against a nevirapine-resistant virus, HIV-1(IIIB-R). The primary hit, a thiazolidenebenzenesulfonamide derivative, possessed good activity. A systematic modification program examining various substituents at the 3-, 4-, and 5-positions on the thiazole ring afforded compounds with enhanced anti-HIV-1 and reverse transcriptase (RT) inhibitory activities. These results confirm the important role of the substituents at these positions and the thiazolidenebenzenesulfonamide motif as a valuable lead series for the next generation NNRTIs.

Benzenesulfonates↗

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↗