Human T-cell leukaemia virus type 1 (HTLV-1) infectivity and cellular transformation

It has been 30 years since a 'new' leukaemia termed adult T-cell leukaemia (ATL) was described in Japan, and more than 25 years since the isolation of the retrovirus, human T-cell leukaemia virus type 1 (HTLV-1), that causes this disease. We discuss HTLV-1 infectivity and how the HTLV-1 Tax oncoprotein initiates transformation by creating a cellular environment favouring aneuploidy and clastogenic DNA damage. We also explore the contribution of a newly discovered protein and RNA on the HTLV-1 minus strand, HTLV-1 basic leucine zipper factor (HBZ), to the maintenance of virus-induced leukaemia.

[1]  K. Sugamura,et al.  Regulatory T cell-like activity of Foxp3+ adult T cell leukemia cells. , 2006, International immunology.

[2]  Samuel H. Wilson,et al.  HTLV-I trans-activator protein, tax, is a trans-repressor of the human beta-polymerase gene. , 1990, Science.

[3]  B. Barbeau,et al.  HBZ, a new important player in the mystery of adult T-cell leukemia. , 2006, Blood.

[4]  L. Ratner,et al.  Human T-Cell Lymphotropic Virus Type 1 Open Reading Frame II-Encoded p30II Is Required for In Vivo Replication: Evidence of In Vivo Reversion , 2004, Journal of Virology.

[5]  T. Misteli,et al.  HTLV-1-encoded p30II is a post-transcriptional negative regulator of viral replication , 2004, Nature Medicine.

[6]  K. Jeang,et al.  Segregation of NF-κB activation through NEMO/IKKγ by Tax and TNFα: implications for stimulus-specific interruption of oncogenic signaling , 2003, Oncogene.

[7]  M. Matsuoka,et al.  Persistent clonal proliferation of human T-lymphotropic virus type I-infected cells in vivo. , 1997, Cancer research.

[8]  O. Pybus,et al.  The low evolutionary rate of human T-cell lymphotropic virus type-1 confirmed by analysis of vertical transmission chains. , 2003, Molecular biology and evolution.

[9]  M. Aboud,et al.  Functional inactivation of p53 by human T-cell leukemia virus type 1 Tax protein: mechanisms and clinical implications. , 2006, Carcinogenesis.

[10]  M. Tomonaga,et al.  Constitutive Activation of NF-κB in Primary Adult T-Cell Leukemia Cells , 1999 .

[11]  G. Wahl,et al.  c-Myc can induce DNA damage, increase reactive oxygen species, and mitigate p53 function: a mechanism for oncogene-induced genetic instability. , 2002, Molecular cell.

[12]  M. Gossen,et al.  Stimulation of Cyclin-Dependent Kinase Activity and G1- to S-Phase Transition in Human Lymphocytes by the Human T-Cell Leukemia/Lymphotropic Virus Type 1 Tax Protein , 1998, Journal of Virology.

[13]  R. Gallo.  The discovery of the first human retrovirus: HTLV-1 and HTLV-2 , 2005, Retrovirology.

[14]  L. Ratner,et al.  Human T-Lymphotropic Virus Type 1 Mitochondrion-Localizing Protein p13II Is Required for Viral Infectivity In Vivo , 2006, Journal of Virology.

[15]  K. Nagashima,et al.  Involvement of Crm1 in Hepatitis B Virus X Protein-Induced Aberrant Centriole Replication and Abnormal Mitotic Spindles , 2003, Molecular and Cellular Biology.

[16]  H. Koeffler,et al.  Longitudinal inhibition of PI3K/Akt/mTOR signaling by LY294002 and rapamycin induces growth arrest of adult T-cell leukemia cells. , 2007, Leukemia research.

[17]  K. W. Kim,et al.  Targeting the Akt/mammalian target of rapamycin pathway for radiosensitization of breast cancer , 2006, Molecular Cancer Therapeutics.

[18]  H. Koeffler,et al.  Longitudinal inhibition of PI 3 K / Akt / mTOR signaling by LY 294002 and rapamycin induces growth arrest of adult T-cell leukemia cells , 2006 .

[19]  N. Mori,et al.  Elevated expression of CD30 in adult T-cell leukemia cell lines: possible role in constitutive NF-κB activation , 2005, Retrovirology.

[20]  Erich A. Nigg,et al.  Centrosome aberrations: cause or consequence of cancer progression? , 2002, Nature Reviews Cancer.

[21]  Yoichi Taya,et al.  HTLV-1 Tax oncoprotein represses the p53-mediated trans-activation function through coactivator CBP sequestration , 2000, Oncogene.

[22]  S. Philpott,et al.  Defective DNA repair in cells with human T-cell leukemia/bovine leukemia viruses: role of tax gene. , 1999, Journal of the National Cancer Institute.

[23]  W. Ding,et al.  Endoplasmic Reticulum and cis-Golgi Localization of Human T-Lymphotropic Virus Type 1 p12I: Association with Calreticulin and Calnexin , 2001, Journal of Virology.

[24]  Joshua Arnold,et al.  Enhancement of infectivity and persistence in vivo by HBZ, a natural antisense coded protein of HTLV-1. , 2006, Blood.

[25]  R. Berro,et al.  The HTLV-I Tax oncoprotein targets the retinoblastoma protein for proteasomal degradation , 2005, Oncogene.

[26]  W. Gerald,et al.  MAD2 haplo-insufficiency causes premature anaphase and chromosome instability in mammalian cells , 2001, Nature.

[27]  Hongtao Yu,et al.  HTLV-I Tax directly binds the Cdc20-associated anaphase-promoting complex and activates it ahead of schedule. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[28]  S. Wain-Hobson,et al.  Persistent oligoclonal expansion of human T-cell leukemia virus type 1-infected circulating cells in patients with Tropical spastic paraparesis/HTLV-1 associated myelopathy , 1998, Oncogene.

[29]  H. Williams,et al.  Healing of broken human chromosomes by the addition of telomeric repeats. , 1994, American journal of human genetics.

[30]  A. Ido,et al.  Telomerase activity and telomere length as prognostic factors of adult T-cell leukemia , 2005, Leukemia & lymphoma.

[31]  M. Matsuoka,et al.  Silencing of human T-cell leukemia virus type I gene transcription by epigenetic mechanisms , 2005, Retrovirology.

[32]  M. Tomonaga,et al.  Allogeneic stem-cell transplantation with reduced conditioning intensity as a novel immunotherapy and antiviral therapy for adult T-cell leukemia/lymphoma. , 2005, Blood.

[33]  K. Jeang,et al.  Modulation of nuclear factor-ϰB by human T cell leukemia virus type 1 tax protein , 2006, Immunologic research.

[34]  M. Matsuoka,et al.  Involvement of IL-2/IL-2R system activation by parasite antigen in polyclonal expansion of CD4+25+ HTLV-1-infected T-cells in human carriers of both HTLV-1 and S. stercoralis , 2002, Oncogene.

[35]  J. Okamura,et al.  Graft-versus-Tax Response in Adult T-Cell Leukemia Patients after Hematopoietic Stem Cell Transplantation , 2004, Cancer Research.

[36]  H. Saya,et al.  Centrosome amplification in adult T‐cell leukemia and human T‐cell leukemia virus type 1 Tax‐induced human T cells , 2006, Cancer science.

[37]  K. Jeang,et al.  Two discrete events, human T-cell leukemia virus type I Tax oncoprotein expression and a separate stress stimulus, are required for induction of apoptosis in T-cells , 2004, Retrovirology.

[38]  E. Murphy,et al.  Global epidemiology of HTLV-I infection and associated diseases , 2005, Oncogene.

[39]  M. Allday,et al.  Epstein-Barr Virus-Induced Resistance to Drugs That Activate the Mitotic Spindle Assembly Checkpoint in Burkitt's Lymphoma Cells , 2006, Journal of Virology.

[40]  A. Schneeweiss,et al.  Centrosomal aberrations in primary invasive breast cancer are associated with nodal status and hormone receptor expression , 2003, International journal of cancer.

[41]  M. Matsuoka,et al.  Rapid quantification of HTLV‐I provirus load: Detection of monoclonal proliferation of HTLV‐I‐infected cells among blood donors , 1999, International Journal of Cancer.

[42]  K. Yamaguchi,et al.  Concurrence of lymphoma type adult T‐cell leukemia in three sisters , 1985, Cancer.

[43]  S. Shirahama,et al.  Evaluation of adult T‐cell leukemia/lymphoma incidence and its impact on non‐Hodgkin lymphoma incidence in southwestern Japan , 2000, International journal of cancer.

[44]  Karl Münger,et al.  Mechanisms of genomic instability in human cancer: Insights from studies with human papillomavirus oncoproteins , 2004, International journal of cancer.

[45]  K. Jeang,et al.  Prevalent Loss of Mitotic Spindle Checkpoint in Adult T-cell Leukemia Confers Resistance to Microtubule Inhibitors* , 2002, The Journal of Biological Chemistry.

[46]  K. Jeang,et al.  Damaged DNA and Miscounted Chromosomes: Human T Cell Leukemia Virus Type I Tax Oncoprotein and Genetic Lesions in Transformed Cells , 2002, Journal of Biomedical Science.

[47]  M. Matsuoka,et al.  Two types of defective human T-lymphotropic virus type I provirus in adult T-cell leukemia. , 1996, Blood.

[48]  T. Akiyama,et al.  PDZ domain-binding motif of human T-cell leukemia virus type 1 Tax oncoprotein augments the transforming activity in a rat fibroblast cell line. , 2004, Virology.

[49]  M. Yoshida,et al.  Down-regulation of the INK4 family of cyclin-dependent kinase inhibitors by tax protein of HTLV-1 through two distinct mechanisms. , 1999, Virology.

[50]  K. Jeang,et al.  Physical Interaction of Human T-Cell Leukemia Virus Type 1 Tax with Cyclin-Dependent Kinase 4 Stimulates the Phosphorylation of Retinoblastoma Protein , 2002, Molecular and Cellular Biology.

[51]  F. Kashanchi,et al.  Transcriptional Up-Regulation of the Cyclin D2 Gene and Acquisition of New Cyclin-Dependent Kinase Partners in Human T-Cell Leukemia Virus Type 1-Infected Cells , 1999, Journal of Virology.

[52]  C. Sardet,et al.  Activation of E2F-mediated Transcription by Human T-cell Leukemia Virus Type I Tax Protein in a p16 INK4A -negative T-cell Line* , 1998, The Journal of Biological Chemistry.

[53]  Y. Tanaka,et al.  Differential transactivation of the intercellular adhesion molecule 1 gene promoter by Tax1 and Tax2 of human T-cell leukemia viruses , 1996, Journal of virology.

[54]  K. Jeang,et al.  Abnormal centrosome amplification in cells through the targeting of Ran-binding protein-1 by the human T cell leukemia virus type-1 Tax oncoprotein. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[55]  T. Akiyama,et al.  Tax oncoprotein of HTLV-1 binds to the human homologue of Drosophila discs large tumor suppressor protein, hDLG, and perturbs its function in cell growth control , 1999, Oncogene.

[56]  K. Münger,et al.  Centrosome abnormalities and genomic instability induced by human papillomavirus oncoproteins. , 2003, Progress in cell cycle research.

[57]  F. Kashanchi,et al.  The role of cyclin D2 and p21/waf1 in human T-cell leukemia virus type 1 infected cells , 2004, Retrovirology.

[58]  K Wheatley,et al.  The importance of diagnostic cytogenetics on outcome in AML: analysis of 1,612 patients entered into the MRC AML 10 trial. The Medical Research Council Adult and Children's Leukaemia Working Parties. , 1998, Blood.

[59]  Mitsuhiro Osame,et al.  Spread of HTLV-I Between Lymphocytes by Virus-Induced Polarization of the Cytoskeleton , 2003, Science.

[60]  S. S. Lee,et al.  Binding of human virus oncoproteins to hDlg/SAP97, a mammalian homolog of the Drosophila discs large tumor suppressor protein. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[61]  M. Salemi,et al.  Dating the origin of the African human T-cell lymphotropic virus type-i (HTLV-I) subtypes. , 2001, Molecular biology and evolution.

[62]  K. Shimotohno,et al.  Expression of cell-cycle regulatory genes in HTLV-I infected T-cell lines: possible involvement of Tax1 in the altered expression of cyclin D2, p18Ink4 and p21Waf1/Cip1/Sdi1. , 1996, Oncogene.

[63]  廣仲 紀子.  Tax-independent constitutive IκB kinase activation in adult T-cell leukemia cells , 2005 .

[64]  M. Matsuoka,et al.  De Novo Human T-Cell Leukemia Virus Type 1 Infection of Human Lymphocytes in NOD-SCID, Common γ-Chain Knockout Mice , 2006, Journal of Virology.

[65]  Kuan-Teh Jeang,et al.  Human T Cell Leukemia Virus Type 1 Oncoprotein Tax Targets the Human Mitotic Checkpoint Protein MAD1 , 1998, Cell.

[66]  K. Yamaguchi,et al.  Dual targeting of transformed and untransformed HTLV-1-infected T cells by DHMEQ, a potent and selective inhibitor of NF-kappaB, as a strategy for chemoprevention and therapy of adult T-cell leukemia. , 2005, Blood.

[67]  Jun-ichirou Yasunaga,et al.  HTLV-I basic leucine zipper factor gene mRNA supports proliferation of adult T cell leukemia cells. , 2006, Proceedings of the National Academy of Sciences of the United States of America.

[68]  K. Jeang,et al.  Inactivation of hTERT transcription by Tax , 2003, Oncogene.

[69]  Yoshiya Tanaka,et al.  Reduced expression of human mismatch repair genes in adult T‐cell leukemia , 2005, American journal of hematology.

[70]  J. Ward,et al.  Heterozygous deletion of mitotic arrest-deficient protein 1 (MAD1) increases the incidence of tumors in mice. , 2007, Cancer research.

[71]  K. Yamaguchi,et al.  5′-Long Terminal Repeat-Selective CpG Methylation of Latent Human T-Cell Leukemia Virus Type 1 Provirus In Vitro and In Vivo , 2002, Journal of Virology.

[72]  K. Jeang,et al.  Human T-cell leukemia virus type I at age 25: a progress report. , 2005, Cancer research.

[73]  C. Croce,et al.  Frequent deletions and down-regulation of micro- RNA genes miR15 and miR16 at 13q14 in chronic lymphocytic leukemia , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[74]  C. Devaux,et al.  HBZ interacts with JunD and stimulates its transcriptional activity , 2004, FEBS letters.

[75]  F. Ruscetti,et al.  GLUT 1 Is Not the Primary Binding Receptor but Is Associated with Cell-to-Cell Transmission of Human T-Cell Leukemia Virus Type 1 , 2007 .

[76]  T. Akiyama,et al.  Binding of APC to the Human Homolog of the Drosophila Discs Large Tumor Suppressor Protein , 1996, Science.

[77]  M. Piechaczyk,et al.  The HBZ Factor of Human T-cell Leukemia Virus Type I Dimerizes with Transcription Factors JunB and c-Jun and Modulates Their Transcriptional Activity* , 2003, Journal of Biological Chemistry.

[78]  W. Heneine,et al.  Emergence of unique primate T-lymphotropic viruses among central African bushmeat hunters , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[79]  M. Matsuoka,et al.  Preferential selection of human T-cell leukemia virus type I provirus integration sites in leukemic versus carrier states. , 2005, Blood.

[80]  S. Yamaoka,et al.  Activation of NF-κB by HTLV-I and implications for cell transformation , 2005, Oncogene.

[81]  M. Tomonaga,et al.  A new G‐CSF‐supported combination chemotherapy, LSG15, for adult T‐cell leukaemia‐lymphoma: Japan Clinical Oncology Group Study 9303 , 2001, British journal of haematology.

[82]  Yoichi Iwanaga,et al.  Ku protein as a potential human T-cell leukemia virus type 1 (HTLV-1) Tax target in clastogenic chromosomal instability of mammalian cells , 2005, Retrovirology.

[83]  K. Shimotohno,et al.  Characterization of T cells immortalized by Tax1 of human T-cell leukemia virus type 1. , 1995, Blood.

[84]  M. Biard-Piechaczyk,et al.  The Complementary Strand of the Human T-Cell Leukemia Virus Type 1 RNA Genome Encodes a bZIP Transcription Factor That Down-Regulates Viral Transcription , 2002, Journal of Virology.

[85]  K. Jeang,et al.  Clastogenic Effect of the Human T-cell Leukemia Virus Type I Tax Oncoprotein Correlates with Unstabilized DNA Breaks* , 2000, The Journal of Biological Chemistry.

[86]  F. Ruscetti,et al.  GLUT1 Is Not the Primary Binding Receptor but Is Associated with Cell-to-Cell Transmission of Human T-Cell Leukemia Virus Type 1 , 2006, Journal of Virology.

[87]  S. Landry,et al.  HTLV-I antisense transcripts initiating in the 3'LTR are alternatively spliced and polyadenylated , 2006, Retrovirology.

[88]  Y. Kodera,et al.  Improved outcome of adult T cell leukemia/lymphoma with allogeneic hematopoietic stem cell transplantation , 2001, Bone Marrow Transplantation.

[89]  S. Jacobson,et al.  Free Major Histocompatibility Complex Class I Heavy Chain Is Preferentially Targeted for Degradation by Human T-Cell Leukemia/Lymphotropic Virus Type 1 p12I Protein , 2001, Journal of Virology.

[90]  Renaud Mahieux,et al.  Inactivation of p53 by Human T-Cell Lymphotropic Virus Type 1 Tax Requires Activation of the NF-κB Pathway and Is Dependent on p53 Phosphorylation , 2000, Molecular and Cellular Biology.

[91]  L. Liotta,et al.  Centrosome defects can account for cellular and genetic changes that characterize prostate cancer progression. , 2001, Cancer research.

[92]  Peter J. Bryant,et al.  The discs-large tumor suppressor gene of Drosophila encodes a guanylate kinase homolog localized at septate junctions , 1991, Cell.

[93]  H. Shigematsu,et al.  Correlation of telomerase activity with development and progression of adult T-cell leukemia. , 1998, Leukemia research.

[94]  K. Jeang,et al.  Human T-cell leukemia virus type 1 Tax releases cell cycle arrest induced by p16INK4a , 1997, Journal of virology.

[95]  P. Rudge,et al.  Zidovudine plus lamivudine in Human T-Lymphotropic Virus type-I-associated myelopathy: a randomised trial , 2006, Retrovirology.

[96]  M. Yoshida,et al.  HTLV‐1 Tax protein interacts with cyclin‐dependent kinase inhibitor p16INK4A and counteracts its inhibitory activity towards CDK4. , 1996, The EMBO journal.

[97]  M. Matsuoka.  Human T-cell leukemia virus type I (HTLV-I) infection and the onset of adult T-cell leukemia (ATL) , 2005, Retrovirology.

[98]  Y. Kuo,et al.  Activation of the anaphase promoting complex by HTLV‐1 tax leads to senescence , 2006, The EMBO journal.

[99]  M. Matsuoka,et al.  Proteasome inhibitor, bortezomib, potently inhibits the growth of adult T-cell leukemia cells both in vivo and in vitro , 2004, Leukemia.

[100]  J. Brady,et al.  Human T-cell leukemia virus type 1 Tax interacts with Chk1 and attenuates DNA-damage induced G2 arrest mediated by Chk1 , 2004, Oncogene.

[101]  L. Ratner,et al.  Selective ablation of human T-cell lymphotropic virus type 1 p12I reduces viral infectivity in vivo. , 1998, Blood.

[102]  G. Morin.  Recognition of a chromosome truncation site associated with α-thalassaemia by human telomerase , 1991, Nature.

[103]  O John Semmes,et al.  The HTLV-1 tax oncoprotein attenuates DNA damage induced G1 arrest and enhances apoptosis in p53 null cells. , 2003, Virology.

[104]  Yuetsu Tanaka,et al.  Human T-lymphotropic Virus, Type 1, Tax Protein Triggers Microtubule Reorientation in the Virological Synapse* , 2005, Journal of Biological Chemistry.

[105]  M. Tomonaga,et al.  DNA aneuploidy of adult T-cell leukemia cells. , 1994, Leukemia research.

[106]  T. Ichinohe,et al.  Thymus-derived leukemia-lymphoma in mice transgenic for the Tax gene of human T-lymphotropic virus type I , 2006, Nature Medicine.

[107]  K. Jeang,et al.  The retroviral oncoprotein Tax targets the coiled-coil centrosomal protein TAX1BP2 to induce centrosome overduplication , 2006, Nature Cell Biology.

[108]  Jingxia Li,et al.  PI-3 K and Akt are mediators of AP-1 induction by 5-MCDE in mouse epidermal Cl 41 cells , 2009 .

[109]  M. Lairmore,et al.  Enhancement of LFA-1-Mediated T Cell Adhesion by Human T Lymphotropic Virus Type 1 p12I1 , 2006, The Journal of Immunology.

[110]  J. Brady,et al.  Activated AKT regulates NF-κB activation, p53 inhibition and cell survival in HTLV-1-transformed cells , 2005, Oncogene.

[111]  E. Harhaj,et al.  Retroviral oncoprotein Tax induces processing of NF‐κB2/p100 in T cells: evidence for the involvement of IKKα , 2001 .

[112]  W. Lingle,et al.  Centrosome Amplification and the Origin of Chromosomal Instability in Breast Cancer , 2004, Journal of Mammary Gland Biology and Neoplasia.

[113]  Yan Shi,et al.  Potent and selective inhibitors of Akt kinases slow the progress of tumors in vivo , 2005, Molecular Cancer Therapeutics.

[114]  S. Calattini,et al.  Discovery of a new human T-cell lymphotropic virus (HTLV-3) in Central Africa , 2005, Retrovirology.

[115]  K. Jeang,et al.  Role for Akt/Protein Kinase B and Activator Protein-1 in Cellular Proliferation Induced by the Human T-cell Leukemia Virus Type 1 Tax Oncoprotein* , 2006, Journal of Biological Chemistry.

[116]  Birthe Müller,et al.  The HTLV-1 Tax protein binding domain of cyclin-dependent kinase 4 (CDK4) includes the regulatory PSTAIRE helix , 2005, Retrovirology.

[117]  D. Derse,et al.  Human T-Cell Leukemia Virus Type 1 Tax Protein Down-Regulates Pre-T-Cell Receptor Alpha Gene Transcription in Human Immature Thymocytes , 2006, Journal of Virology.

[118]  M. Sitbon,et al.  The Ubiquitous Glucose Transporter GLUT-1 Is a Receptor for HTLV , 2003, Cell.

[119]  I. Lemasson,et al.  Transcriptional activation of the vascular cell adhesion molecule-1 gene in T lymphocytes expressing human T-cell leukemia virus type 1 Tax protein , 1997, Journal of virology.

[120]  W. Ding,et al.  Human T-Lymphotropic Virus Type 1 p30IIFunctions as a Transcription Factor and Differentially Modulates CREB-Responsive Promoters , 2000, Journal of Virology.

[121]  K. Ohtani,et al.  Molecular mechanism of cell cycle progression induced by the oncogene product Tax of human T-cell leukemia virus type I , 2001, Oncogene.

[122]  Mitsuhiro Osame,et al.  Cellular immune response to HTLV-1 , 2005, Oncogene.

[123]  M. Seto,et al.  Human T-cell leukemia virus minus strand transcription in infected T-cells. , 1989, Biochemical and biophysical research communications.

[124]  P. Green,et al.  Human T-Cell Leukemia Virus Type 1 Expressing Nonoverlapping Tax and Rex Genes Replicates and Immortalizes Primary Human T Lymphocytes but Fails To Replicate and Persist In Vivo , 2005, Journal of Virology.

[125]  Jingxia Li,et al.  PI-3K and Akt are mediators of AP-1 induction by 5-MCDE in mouse epidermal Cl41 cells , 2004, The Journal of Cell Biology.

[126]  Masahito Hayashi,et al.  Induction of ICAM‐1 and LFA‐3 by Tax1 of human T‐cell leukemia virus type 1 and mechanism of down‐regulation of ICAM‐1 or LFA‐1 in adult‐T‐cell‐leukemia cell lines , 1995, International journal of cancer.

[127]  K. Jeang,et al.  Molecular mechanisms of cellular transformation by HTLV-1 Tax , 2005, Oncogene.

[128]  L. Gazzolo,et al.  The Human T Cell Leukemia/Lymphotropic Virus Type 1 Tax Protein Represses MyoD-dependent Transcription by Inhibiting MyoD-binding to the KIX Domain of p300 , 2000, The Journal of Biological Chemistry.

[129]  A. Wilkie,et al.  A truncated human chromosome 16 associated with α thalassaemia is stabilized by addition of telomeric repeat (TTAGGG)n , 1990, Nature.

[130]  Yuetsu Tanaka,et al.  Engagement of specific T-cell surface molecules regulates cytoskeletal polarization in HTLV-1-infected lymphocytes. , 2005, Blood.

[131]  M. Matsuoka,et al.  Impaired production of naive T lymphocytes in human T-cell leukemia virus type I-infected individuals: its implications in the immunodeficient state. , 2001, Blood.

[132]  N. Mori,et al.  Tax-independent constitutive IkappaB kinase activation in adult T-cell leukemia cells. , 2004, Neoplasia.

[133]  K. Karube,et al.  Expression of FoxP3, a key molecule in CD4+CD25+ regulatory T cells, in adult T‐cell leukaemia/lymphoma cells , 2004, British journal of haematology.

[134]  D. Rasnick.  Aneuploidy theory explains tumor formation, the absence of immune surveillance, and the failure of chemotherapy. , 2002, Cancer genetics and cytogenetics.

[135]  S. Bao,et al.  The activation of Akt/PKB signaling pathway and cell survival , 2005, Journal of cellular and molecular medicine.

[136]  K. Jeang,et al.  Human T-Cell Leukemia Virus Type 1 Tax and Cell Cycle Progression: Role of Cyclin D-cdk and p110Rb , 1998, Molecular and Cellular Biology.

[137]  K. Jeang,et al.  Evidence for NF-κB- and CBP-Independent Repression of p53's Transcriptional Activity by Human T-Cell Leukemia Virus Type 1 Tax in Mouse Embryo and Primary Human Fibroblasts , 2005, Journal of Virology.

[138]  S. Izumo,et al.  Existence of escape mutant in HTLV-I tax during the development of adult T-cell leukemia. , 2001, Blood.

[139]  Mitsuaki Yoshida.  Discovery of HTLV-1, the first human retrovirus, its unique regulatory mechanisms, and insights into pathogenesis , 2005, Oncogene.

[140]  K. Takatsuki,et al.  Discovery of adult T-cell leukemia , 2005, Retrovirology.

[141]  Yuetsu Tanaka,et al.  Inactivation of tumor suppressor Dlg1 augments transformation of a T-cell line induced by human T-cell leukemia virus type 1 Tax protein , 2006 .

[142]  K. Jeang,et al.  Characterization of Regions in hsMAD1 Needed for Binding hsMAD2 , 2002, The Journal of Biological Chemistry.

[143]  S. J. Marriott,et al.  p53-independent induction of apoptosis by the HTLV-I tax protein following UV irradiation. , 2001, Virology.

[144]  A. Musacchio,et al.  The spindle checkpoint: structural insights into dynamic signalling , 2002, Nature Reviews Molecular Cell Biology.

[145]  P. Couppié,et al.  Increased expression of telomere length regulating factors TRF1, TRF2 and TIN2 in patients with adult T‐cell leukemia , 2006, International journal of cancer.

[146]  J. Zack,et al.  Human T-cell leukemia virus infection of human hematopoietic progenitor cells: maintenance of virus infection during differentiation in vitro and in vivo , 1996, Journal of virology.

[147]  C. Bloomfield,et al.  Pretreatment cytogenetic abnormalities are predictive of induction success, cumulative incidence of relapse, and overall survival in adult patients with de novo acute myeloid leukemia: results from Cancer and Leukemia Group B (CALGB 8461). , 2002, Blood.

[148]  S. Wain-Hobson,et al.  Clonal expansion of human T-cell leukemia virus type I-infected cells in asymptomatic and symptomatic carriers without malignancy , 1995, Journal of virology.

[149]  T. Akiyama,et al.  The APC-hDLG complex negatively regulates cell cycle progression from the G0/G1 to S phase , 2000, Oncogene.

[150]  W. Heneine,et al.  Ancient Origin and Molecular Features of the Novel Human T-Lymphotropic Virus Type 3 Revealed by Complete Genome Analysis , 2006, Journal of Virology.

[151]  M. Matsuoka,et al.  Genetic and epigenetic inactivation of tax gene in adult T‐cell leukemia cells , 2004, International journal of cancer.