Human T-lymphotropic virus 1


Alias: Human lymphotropic virus type I, human T-lymphotropic virus type I HTLV-I, human T-lymphotropic virus type 1 HTLV-1, human T-cell lymphotropic virus type 1, HTLV-1, human T-cell lymphoma/leukemia virus type I HTLV-I, human T-cell leukemia/lymphotropic virus type I HTLV-I, human T-cell leukemia/lymphoma virus type I HTLV-I, human T-cell leukemia virus type 1 HTLV-1, human T-cell leukemia virus I, human T cell lymphotropic virus type I HTLV-I, human T cell leukemia virus type 1 HTLV-1, Human adult T-cell leukemia virus, Human T-cell lymphotropic virus type I, Human T-cell lymphotropic virus type 1, Human T-cell lymphotropic virus 1, Human T-cell leukemia virus type I HTLV-I, Human T-cell leukemia virus type I, Human T-cell leukemia virus type 1, Human T cell leukemia virus type 1, HTLV-1, HTLV-I, human T cell leukemia virus type I HTLV-I, human T-cell leukemia virus-1 HTLV-1, Human T-cell lymphotrophic virus type 1, Human T-lymphotropic virus type 1

Top Publications

  1. Yasunaga J, Lin F, Lu X, Jeang K. Ubiquitin-specific peptidase 20 targets TRAF6 and human T cell leukemia virus type 1 tax to negatively regulate NF-kappaB signaling. J Virol. 2011;85:6212-9 pubmed publisher
    ..Infection by human T cell leukemia virus type 1 (HTLV-1) causes a fatal hematopoietic malignancy termed adult T cell leukemia (ATL)...
  2. Arpin André C, Mesnard J. The PDZ domain-binding motif of the human T cell leukemia virus type 1 tax protein induces mislocalization of the tumor suppressor hScrib in T cells. J Biol Chem. 2007;282:33132-41 pubmed
    ..In this regard, the oncogenic potential of the human T cell leukemia virus type 1 Tax protein correlates with its binding capacity to the tumor suppressor hDlg...
  3. Jeong S, Ryo A, Yamamoto N. The prolyl isomerase Pin1 stabilizes the human T-cell leukemia virus type 1 (HTLV-1) Tax oncoprotein and promotes malignant transformation. Biochem Biophys Res Commun. 2009;381:294-9 pubmed publisher
    ..Our current study demonstrates an important role for Pin1 in the post-translational regulation of Tax and suggests that the targeting of Pin1 may offer a new insight into the pathogenesis of HTLV-1 related diseases...
  4. Pise Masison C, Jeong S, Brady J. Human T cell leukemia virus type 1: the role of Tax in leukemogenesis. Arch Immunol Ther Exp (Warsz). 2005;53:283-96 pubmed
    b>Human T cell leukemia virus type 1 (HTLV-1) is a complex human retrovirus which is the causative agent of adult T cell leukemia (ATL). ATL occurs in about 4% of carriers and develops after a long latent period...
  5. Kehn K, Fuente C, Strouss K, Berro R, Jiang H, Brady J, et al. The HTLV-I Tax oncoprotein targets the retinoblastoma protein for proteasomal degradation. Oncogene. 2005;24:525-40 pubmed
    ..Therefore, we propose a model whereby Tax targets Rb to the proteasome by acting as a molecular bridge bringing Rb into contact with the proteasome for degradation. ..
  6. Bellon M, Baydoun H, Yao Y, Nicot C. HTLV-I Tax-dependent and -independent events associated with immortalization of human primary T lymphocytes. Blood. 2010;115:2441-8 pubmed publisher
    ..These data provide a better understanding of Tax functions in human T cells, and highlight the limitations of Tax, suggesting that other viral proteins are key to T-cell transformation and development of adult T-cell leukemia. ..
  7. Ishioka K, Higuchi M, Takahashi M, Yoshida S, Oie M, Tanaka Y, 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. Retrovirology. 2006;3:71 pubmed
    ..The interaction of human T-cell leukemia virus type 1 (HTLV-1) Tax1 protein with the tumor suppressor Dlg1 is correlated with cellular transformation...
  8. Winter H, Marriott S. Human T-cell leukemia virus type 1 Tax enhances serum response factor DNA binding and alters site selection. J Virol. 2007;81:6089-98 pubmed
    ..These results suggest that Tax activates SRF-responsive transcription by enhancing its binding affinity to multiple different SRE sequences. ..
  9. Ram rez J, Nyborg J. Molecular characterization of HTLV-1 Tax interaction with the KIX domain of CBP/p300. J Mol Biol. 2007;372:958-69 pubmed publisher
    ..We also show that MLL competes with Tax for KIX binding, suggesting a novel mechanism of Tax oncogenesis in which normal MLL function is disrupted by Tax...

More Information


  1. Fryrear K, Guo X, Kerscher O, Semmes O. The Sumo-targeted ubiquitin ligase RNF4 regulates the localization and function of the HTLV-1 oncoprotein Tax. Blood. 2012;119:1173-81 pubmed publisher
    ..These results provide important new insight into STUbL-mediated pathways that regulate the subcellular localization and functional dynamics of viral oncogenes. ..
  2. Toufaily C, Landry S, Leib Mösch C, Rassart E, Barbeau B. Activation of LTRs from different human endogenous retrovirus (HERV) families by the HTLV-1 tax protein and T-cell activators. Viruses. 2011;3:2146-59 pubmed publisher
    ..Our results thus demonstrated that HTLV-1 Tax activates several HERV LTRs. This raises the possibility that upregulated HERV expression could be involved in diseases associated with HTLV-1 infection...
  3. Saito K, Saito M, Taniura N, Okuwa T, Ohara Y. Activation of the PI3K-Akt pathway by human T cell leukemia virus type 1 (HTLV-1) oncoprotein Tax increases Bcl3 expression, which is associated with enhanced growth of HTLV-1-infected T cells. Virology. 2010;403:173-80 pubmed publisher
    ..Our results indicate that the overexpression of Bcl3 in HTLV-1-infected T cells is regulated not only by transcriptional but also by post-transcriptional mechanisms, and is involved in overgrowth of HTLV-1-infected T cells...
  4. Pichler K, Kattan T, Gentzsch J, Kress A, Taylor G, Bangham C, et al. Strong induction of 4-1BB, a growth and survival promoting costimulatory receptor, in HTLV-1-infected cultured and patients' T cells by the viral Tax oncoprotein. Blood. 2008;111:4741-51 pubmed publisher
    ..Thus, 4-1BB up-regulation by Tax could contribute to growth, survival, and clonal expansion of the infected cells during persistence and disease. ..
  5. Tomita M, Tanaka Y, Mori N. MicroRNA miR-146a is induced by HTLV-1 tax and increases the growth of HTLV-1-infected T-cells. Int J Cancer. 2012;130:2300-9 pubmed publisher
    ..Moreover, overexpression of miR-146a enhanced the growth of an HTLV-1-infected T-cell line. Our findings suggest that miR-146a is a potentially suitable therapeutic target of ATL...
  6. Shoji T, Higuchi M, Kondo R, Takahashi M, Oie M, Tanaka Y, et al. Identification of a novel motif responsible for the distinctive transforming activity of human T-cell leukemia virus (HTLV) type 1 Tax1 protein from HTLV-2 Tax2. Retrovirology. 2009;6:83 pubmed publisher
    ..This distinction was mediated by at least two Tax1 specific functions, an interaction with host cellular factors through the PDZ domain binding motif (PBM) and the activation of NF-kappa B2 (NF-kappa B2)/p100...
  7. Nejmeddine M, Negi V, Mukherjee S, Tanaka Y, Orth K, Taylor G, et al. HTLV-1-Tax and ICAM-1 act on T-cell signal pathways to polarize the microtubule-organizing center at the virological synapse. Blood. 2009;114:1016-25 pubmed publisher
    ..The results also reveal differences in the signaling pathways used to trigger MTOC polarization between the immunologic synapse and the virological synapse. ..
  8. Gupta S, Guo X, Durkin S, Fryrear K, Ward M, Semmes O. Human T-cell leukemia virus type 1 Tax oncoprotein prevents DNA damage-induced chromatin egress of hyperphosphorylated Chk2. J Biol Chem. 2007;282:29431-40 pubmed
    ..We propose that Tax binding via the Chk2 kinase domain sequesters phosphorylated Chk2 within chromatin, thus hindering chromatin egress and appropriate response to DNA damage. ..
  9. Lemasson I, Polakowski N, Laybourn P, Nyborg J. Tax-dependent displacement of nucleosomes during transcriptional activation of human T-cell leukemia virus type 1. J Biol Chem. 2006;281:13075-82 pubmed
    ..These results support a model in which nucleosomes are depleted from the LTR and transcribed region during Tax-mediated transcriptional activation and correlate RNA polymerase II recruitment with nucleosome depletion. ..
  10. Alefantis T, Jain P, Ahuja J, Mostoller K, Wigdahl B. HTLV-1 Tax nucleocytoplasmic shuttling, interaction with the secretory pathway, extracellular signaling, and implications for neurologic disease. J Biomed Sci. 2005;12:961-74 pubmed
    The human T cell leukemia virus type 1 (HTLV-1) oncoprotein Tax interacts with numerous cellular pathways promoting both the survival and pathogenesis of the virus in the human population...
  11. Kusano S, Eizuru Y. Human phospholipid scramblase 1 interacts with and regulates transactivation of HTLV-1 Tax. Virology. 2012;432:343-52 pubmed publisher
    ..PLSCR1 may play an important role in the IFN-mediated repression of Tax-dependent transactivation during HTLV-1 infection...
  12. Higuchi M, Fujii M. Distinct functions of HTLV-1 Tax1 from HTLV-2 Tax2 contribute key roles to viral pathogenesis. Retrovirology. 2009;6:117 pubmed publisher
    ..In this review, we summarize the functions of Tax1 associated with cell survival, cell proliferation, persistent infection as well as pathogenesis. We emphasize special attention to distinctions between Tax1 and Tax2. ..
  13. Bogenberger J, Laybourn P. Human T Lymphotropic Virus Type 1 protein Tax reduces histone levels. Retrovirology. 2008;5:9 pubmed publisher
    ..This study provides a previously unidentified mechanism by which Tax may directly induce chromosomal instability and deregulate gene expression through reduced histone levels. ..
  14. Fu J, Yan P, Li S, Qu Z, Xiao G. Molecular determinants of PDLIM2 in suppressing HTLV-I Tax-mediated tumorigenesis. Oncogene. 2010;29:6499-507 pubmed publisher
    ..These studies dissect functional sequences within PDLIM2 and their distinct roles in Tax regulation. ..
  15. Pichler K, Schneider G, Grassmann R. MicroRNA miR-146a and further oncogenesis-related cellular microRNAs are dysregulated in HTLV-1-transformed T lymphocytes. Retrovirology. 2008;5:100 pubmed publisher
    ..Affecting e.g. proliferation, microRNAs constitute a potential target for viral interference on the way to persistence and transformation. Hence, we explored the interconnections between HTLV-1 and cellular microRNAs...
  16. Lamsoul I, Lodewick J, Lebrun S, Brasseur R, Burny A, Gaynor R, et al. Exclusive ubiquitination and sumoylation on overlapping lysine residues mediate NF-kappaB activation by the human T-cell leukemia virus tax oncoprotein. Mol Cell Biol. 2005;25:10391-406 pubmed
    ..These modifications may result in targets for the treatment of adult T-cell leukemia. ..
  17. Vajente N, Trevisan R, Saggioro D. HTLV-1 Tax protein cooperates with Ras in protecting cells from apoptosis. Apoptosis. 2009;14:153-63 pubmed publisher
    ..As a whole, our findings provide intriguing evidence of a possible link between Ras signaling and Tax capability to counteract apoptosis and to enhance P-CREB levels, and implicates a potential role for Ras in HTLV-1-induced diseases...
  18. Andresen V, Pise Masison C, Sinha Datta U, Bellon M, Valeri V, Washington Parks R, et al. Suppression of HTLV-1 replication by Tax-mediated rerouting of the p13 viral protein to nuclear speckles. Blood. 2011;118:1549-59 pubmed publisher
    ..Further, these results highlight the importance of studying the function of the HTLV-1 viral proteins, not only in isolation, but also in the context of full viral replication...
  19. Xiao G. NF-kappaB activation: Tax sumoylation is out, but what about Tax ubiquitination?. Retrovirology. 2012;9:78 pubmed publisher
    ..Here, we discuss our current understanding of Tax activation of NF-?B, with a focus on the controversies and the challenges that we are facing. ..
  20. Bidoia C, Mazzorana M, Pagano M, Arrigoni G, Meggio F, Pinna L, et al. The pleiotropic protein kinase CK2 phosphorylates HTLV-1 Tax protein in vitro, targeting its PDZ-binding motif. Virus Genes. 2010;41:149-57 pubmed publisher
    ..These results suggest that CK2, whose constitutive activity is often hijacked by viruses to sustain their vital cycle, could modulate Tax-1 oncogenic interactions. ..
  21. Kamoi K, Yamamoto K, Misawa A, Miyake A, Ishida T, Tanaka Y, et al. SUV39H1 interacts with HTLV-1 Tax and abrogates Tax transactivation of HTLV-1 LTR. Retrovirology. 2006;3:5 pubmed
  22. Wäldele K, Silbermann K, Schneider G, Ruckes T, Cullen B, Grassmann R. Requirement of the human T-cell leukemia virus (HTLV-1) tax-stimulated HIAP-1 gene for the survival of transformed lymphocytes. Blood. 2006;107:4491-9 pubmed
    b>Human T cell leukemia virus type 1 (HTLV-1), the cause of adult T cell leukemia (ATL), induces clonal expansion of infected T-cells in nonleukemic individuals and immortalizes T cells in vitro...
  23. Pise Masison C, Brady J. Setting the stage for transformation: HTLV-1 Tax inhibition of p53 function. Front Biosci. 2005;10:919-30 pubmed
    ..This review will concentrate on the ability of Tax to promote cellular proliferation through activation of the NF-kappaB pathway while inhibiting the cell-cycle checkpoint and apoptotic function of the tumor suppressor gene p53. ..
  24. Lodewick J, Lamsoul I, Bex F. Move or die: the fate of the Tax oncoprotein of HTLV-1. Viruses. 2011;3:829-57 pubmed publisher
  25. Koga H, Ohshima T, Shimotohno K. Enhanced activation of tax-dependent transcription of human T-cell leukemia virus type I (HTLV-I) long terminal repeat by TORC3. J Biol Chem. 2004;279:52978-83 pubmed
    ..These results provide important clues toward understanding the molecular mechanism of Tax-dependent transcriptional activation of the HTLV-I LTR. ..
  26. Van Duyne R, Guendel I, Klase Z, Narayanan A, Coley W, Jaworski E, et al. Localization and sub-cellular shuttling of HTLV-1 tax with the miRNA machinery. PLoS ONE. 2012;7:e40662 pubmed publisher
    ..Finally, the changes in cellular miRNA expression in HTLV-1 infected cells can be mimicked by the add back of Drosha or the addition of antagomiRs against the cellular miRNAs which are downregulated by the virus...
  27. Okajima M, Takahashi M, Higuchi M, Ohsawa T, Yoshida S, Yoshida Y, et al. Human T-cell leukemia virus type 1 Tax induces an aberrant clustering of the tumor suppressor Scribble through the PDZ domain-binding motif dependent and independent interaction. Virus Genes. 2008;37:231-40 pubmed publisher
    ..These results suggest that Tax1 through two binding sites induce aberrant clustering of Scribble, thereby altering the functions in HTLV-1-infected cells, which may thus play a role in persistent HTLV-1 infection and the pathogenesis. ..
  28. Lodewick J, Lamsoul I, Polania A, Lebrun S, Burny A, Ratner L, et al. Acetylation of the human T-cell leukemia virus type 1 Tax oncoprotein by p300 promotes activation of the NF-kappaB pathway. Virology. 2009;386:68-78 pubmed publisher
    ..Thus, Tax acetylation favors NF-kappaB activation and might play an important role in HTLV-1-induced cell transformation. ..
  29. Manuel S, Schell T, Acheampong E, Rahman S, Khan Z, Jain P. Presentation of human T cell leukemia virus type 1 (HTLV-1) Tax protein by dendritic cells: the underlying mechanism of HTLV-1-associated neuroinflammatory disease. J Leukoc Biol. 2009;86:1205-16 pubmed publisher
    ..Our studies clearly establish a role for this important immune cell component in HTLV-1 immuno/neuropathogenesis and suggest that modulation of DC functions could be an important tool for therapeutic interventions...
  30. Imai M, Higuchi M, Kawamura H, Yoshita M, Takahashi M, Oie M, et al. Human T cell leukemia virus type 2 (HTLV-2) Tax2 has a dominant activity over HTLV-1 Tax1 to immortalize human CD4+ T cells. Virus Genes. 2013;46:39-46 pubmed publisher
    While human T cell leukemia virus type 1 (HTLV-1) is the causative agent of adult T cell leukemia, a close relative, HTLV-2, is not associated with any leukemia...
  31. Alefantis T, Mostoller K, Jain P, Harhaj E, Grant C, Wigdahl B. Secretion of the human T cell leukemia virus type I transactivator protein tax. J Biol Chem. 2005;280:17353-62 pubmed
    b>Human T cell leukemia virus type I (HTLV-I) is the etiologic agent of adult T cell leukemia and HTLV-I-associated myelopathy/tropical spastic paraparesis...
  32. Dean J, Hashimoto K, Tsuji T, Gautier V, Hall W, Sheehy N. Functional interaction of HTLV-1 tax protein with the POZ domain of the transcriptional repressor BCL6. Oncogene. 2009;28:3723-34 pubmed publisher
    ..This suggests that the expression of BCL6 in HTLV infected cells may contribute to the silencing of viral gene expression and to the long clinical latency associated with HTLV infection...
  33. Huang G, Zhang Z, Jin D. Stimulation of IKK-gamma oligomerization by the human T-cell leukemia virus oncoprotein Tax. FEBS Lett. 2002;531:494-8 pubmed
    ..Taken together, our findings suggest a new model of Tax activation of NF-kappaB, in which Tax interacts with IKK-gamma to stimulate its oligomerization. ..
  34. Kattan T, MacNamara A, Rowan A, Nose H, Mosley A, Tanaka Y, et al. The avidity and lytic efficiency of the CTL response to HTLV-1. J Immunol. 2009;182:5723-9 pubmed publisher
    ..CTL quality determines the position of virus-host equilibrium in persistent HTLV-1 infection. ..
  35. Zhang L, Zhi H, Liu M, Kuo Y, Giam C. Induction of p21(CIP1/WAF1) expression by human T-lymphotropic virus type 1 Tax requires transcriptional activation and mRNA stabilization. Retrovirology. 2009;6:35 pubmed publisher
    ..The possible involvement of Tax-mediated APC/C activation in p21(CIP1/WAF1) mRNA stabilization is discussed. ..
  36. Younis I, Green P. The human T-cell leukemia virus Rex protein. Front Biosci. 2005;10:431-45 pubmed
    ..Herein we summarize the progress made towards understanding Rex function and its role in the HTLV life cycle. ..
  37. Geiger T, Sharma N, Kim Y, Nyborg J. The human T-cell leukemia virus type 1 tax protein confers CBP/p300 recruitment and transcriptional activation properties to phosphorylated CREB. Mol Cell Biol. 2008;28:1383-92 pubmed
    ..The regulation of transcription by pCREB is therefore more complex than is generally recognized, and coregulators, such as Tax, likely play a critical role in the modulation of pCREB function. ..
  38. Shembade N, Harhaj N, Yamamoto M, Akira S, Harhaj E. The human T-cell leukemia virus type 1 Tax oncoprotein requires the ubiquitin-conjugating enzyme Ubc13 for NF-kappaB activation. J Virol. 2007;81:13735-42 pubmed
    ..Collectively, our results reveal that Ubc13 is essential for Tax ubiquitination, its interaction with NEMO, and Tax-mediated NF-kappaB activation...
  39. Gao L, Deng H, Zhao H, Hirbe A, Harding J, Ratner L, et al. HTLV-1 Tax transgenic mice develop spontaneous osteolytic bone metastases prevented by osteoclast inhibition. Blood. 2005;106:4294-302 pubmed publisher
  40. Liu B, Hong S, Tang Z, Yu H, Giam C. HTLV-I Tax directly binds the Cdc20-associated anaphase-promoting complex and activates it ahead of schedule. Proc Natl Acad Sci U S A. 2005;102:63-8 pubmed
    ..Unscheduled activation of APC(Cdc20) by Tax provides an explanation for the mitotic abnormalities in HTLV-I-infected cells and is likely to play an important role in the development of adult T cell leukemia. ..
  41. Merling R, Chen C, Hong S, Zhang L, Liu M, Kuo Y, et al. HTLV-1 Tax mutants that do not induce G1 arrest are disabled in activating the anaphase promoting complex. Retrovirology. 2007;4:35 pubmed
    ..Importantly, the ability of these mutants to activate APC/C is attenuated or abrogated. These data indicate that Tax-induced rapid senescence is causally associated with APC/C activation. ..
  42. Avesani F, Romanelli M, Turci M, Di Gennaro G, Sampaio C, Bidoia C, et al. Association of HTLV Tax proteins with TAK1-binding protein 2 and RelA in calreticulin-containing cytoplasmic structures participates in Tax-mediated NF-?B activation. Virology. 2010;408:39-48 pubmed publisher
    ..Co-expression of RelA and/or TAB2 markedly increased Tax-mediated NF-?B activation. These findings provide new insights into the role of RelA, TAB2 and Tax in the deregulation of the NF-?B pathway...
  43. Harhaj E, Harhaj N, Grant C, Mostoller K, Alefantis T, Sun S, et al. Human T cell leukemia virus type I Tax activates CD40 gene expression via the NF-kappa B pathway. Virology. 2005;333:145-58 pubmed
    The human T cell leukemia virus type I (HTLV-I) is an oncogenic retrovirus that is etiologically linked to the genesis of adult T cell leukemia (ATL) as well as HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP)...
  44. Yoshita M, Higuchi M, Takahashi M, Oie M, Tanaka Y, Fujii M. Activation of mTOR by human T-cell leukemia virus type 1 Tax is important for the transformation of mouse T cells to interleukin-2-independent growth. Cancer Sci. 2012;103:369-74 pubmed publisher
    ..These results suggest that Tax activates the mTOR pathway in T cells, and that this activation plays a crucial role in the growth of HTLV-1-infected T cells when a limited amount of IL-2 is available. ..
  45. Twizere J, Springael J, Boxus M, Burny A, Dequiedt F, Dewulf J, et al. Human T-cell leukemia virus type-1 Tax oncoprotein regulates G-protein signaling. Blood. 2007;109:1051-60 pubmed
    ..Our data indicated that HTLV-1 developed a strategy based on the activation of the SDF-1/CXCR4 axis in the infected cell; this could have tremendous implications for new therapeutic strategies. ..
  46. Zhi H, Yang L, Kuo Y, Ho Y, Shih H, Giam C. NF-?B hyper-activation by HTLV-1 tax induces cellular senescence, but can be alleviated by the viral anti-sense protein HBZ. PLoS Pathog. 2011;7:e1002025 pubmed publisher
    Activation of I-?B kinases (IKKs) and NF-?B by the human T lymphotropic virus type 1 (HTLV-1) trans-activator/oncoprotein, Tax, is thought to promote cell proliferation and transformation...
  47. Bertazzoni U, Turci M, Avesani F, Di Gennaro G, Bidoia C, Romanelli M. Intracellular localization and cellular factors interaction of HTLV-1 and HTLV-2 Tax proteins: similarities and functional differences. Viruses. 2011;3:541-60 pubmed publisher
    ..Special attention will be given to the distinctions between Tax-1 and Tax-2 that likely play an important role in their transactivation activity. ..
  48. Zane L, Sibon D, Legras C, Lachuer J, Wierinckx A, Mehlen P, et al. Clonal expansion of HTLV-1 positive CD8+ cells relies on cIAP-2 but not on c-FLIP expression. Virology. 2010;407:341-51 pubmed publisher
    ..These results support a role for Tax-dependent cIAP-2 expression in preventing the death of naturally infected CD8(+) cells and thereby in their clonal expansion in vivo...
  49. Nakachi S, Nakazato T, Ishikawa C, Kimura R, Mann D, Senba M, et al. Human T-cell leukemia virus type 1 tax transactivates the matrix metalloproteinase 7 gene via JunD/AP-1 signaling. Biochim Biophys Acta. 2011;1813:731-41 pubmed publisher
    ..These results suggest that the induction of MMP-7 by Tax is regulated by JunD and that MMP-7 could facilitate visceral invasion in ATL. This article is part of a Special Issue entitled: 11th European Symposium on Calcium. ..
  50. Ducu R, Dayaram T, Marriott S. The HTLV-1 Tax oncoprotein represses Ku80 gene expression. Virology. 2011;416:1-8 pubmed publisher
    ..The reduction of Ku80 transcription by Tax may deplete the cell of an essential DNA break binding protein, resulting in reduced repair of DNA double strand breaks and accumulation genomic mutations. ..
  51. Jin D, Spencer F, Jeang K. Human T cell leukemia virus type 1 oncoprotein Tax targets the human mitotic checkpoint protein MAD1. Cell. 1998;93:81-91 pubmed
    ..We propose a model of viral transformation in which Tax targets TXBP181, thereby abrogating a mitotic checkpoint. ..
  52. Majone F, Luisetto R, Zamboni D, Iwanaga Y, Jeang K. Ku protein as a potential human T-cell leukemia virus type 1 (HTLV-1) Tax target in clastogenic chromosomal instability of mammalian cells. Retrovirology. 2005;2:45 pubmed
    ..Taken together, our findings suggest Ku80 as a cellular factor targeted by Tax in engendering clastogenic DNA damage. ..
  53. Lee S, Weiss R, Javier R. Binding of human virus oncoproteins to hDlg/SAP97, a mammalian homolog of the Drosophila discs large tumor suppressor protein. Proc Natl Acad Sci U S A. 1997;94:6670-5 pubmed
    ..b>Human T cell leukemia virus type 1 Tax and most oncogenic human papillomavirus E6 oncoproteins also possessed PDZ domain-binding motifs ..
  54. H monnot B, Molle D, Bardy M, Gay B, Laune D, Devaux C, et al. Phosphorylation of the HTLV-1 matrix L-domain-containing protein by virus-associated ERK-2 kinase. Virology. 2006;349:430-9 pubmed publisher
    ..Our data thus support the postulate that phosphorylation of retroviral L-domain proteins is a common feature to retroviruses that participates in the regulation of viral budding...
  55. Baydoun H, Bai X, Shelton S, Nicot C. HTLV-I tax increases genetic instability by inducing DNA double strand breaks during DNA replication and switching repair to NHEJ. PLoS ONE. 2012;7:e42226 pubmed publisher
  56. Baydoun H, Duc Dodon M, Lebrun S, Gazzolo L, Bex F. Regulation of the human T-cell leukemia virus gene expression depends on the localization of regulatory proteins Tax, Rex and p30II in specific nuclear subdomains. Gene. 2007;386:191-201 pubmed
    ..These data support the idea that the transcriptional and post-transcriptional regulation of HTLV-1 gene expression depends on the concentration of select regulatory complexes at specific area of the nucleus. ..
  57. Durkin S, Ward M, Fryrear K, Semmes O. Site-specific phosphorylation differentiates active from inactive forms of the human T-cell leukemia virus type 1 Tax oncoprotein. J Biol Chem. 2006;281:31705-12 pubmed
    ..These results suggest that both positive and negative phosphorylation signals result in the maintenance of a subfraction of Tax as "active" protein. ..
  58. Choudhary G, Ratner L. The HTLV-1 hbz antisense gene indirectly promotes tax expression via down-regulation of p30(II) mRNA. Virology. 2011;410:307-15 pubmed publisher
    ..Mutation of p30(II) overcame the effects of the splice acceptor mutation of hbz, and restored tax expression. Thus, there is a complex interplay of viral regulatory proteins controlling levels of HTLV-1 gene expression...
  59. Wycuff D, Marriott S. The HTLV-I Tax oncoprotein: hyper-tasking at the molecular level. Front Biosci. 2005;10:620-42 pubmed
  60. Abe M, Suzuki H, Nishitsuji H, Shida H, Takaku H. Interaction of human T-cell lymphotropic virus type I Rex protein with Dicer suppresses RNAi silencing. FEBS Lett. 2010;584:4313-8 pubmed publisher
    ..These results suggest that the interaction of Dicer with HTLV-I Rex inhibits Dicer activity and thereby reduces the efficiency of the conversion of shRNA to siRNA. ..
  61. Ho Y, Zhi H, Debiaso D, Philip S, Shih H, Giam C. HTLV-1 tax-induced rapid senescence is driven by the transcriptional activity of NF-?B and depends on chronically activated IKK? and p65/RelA. J Virol. 2012;86:9474-83 pubmed publisher
    ..The senescence checkpoint triggered by Tax is driven by the transcriptional activity of NF-?B, which depends on activated IKK? and p65/RelA...
  62. Okamoto K, Fujisawa J, Reth M, Yonehara S. Human T-cell leukemia virus type-I oncoprotein Tax inhibits Fas-mediated apoptosis by inducing cellular FLIP through activation of NF-kappaB. Genes Cells. 2006;11:177-91 pubmed
    ..Taken together, Tax inhibits Fas-mediated apoptosis by up-regulating c-FLIP expression in HTLV-I-infected cells, and NF-kappaB activity plays an essential role in the up-regulation of c-FLIP. ..
  63. Kinjo T, Ham Terhune J, Peloponese J, Jeang K. Induction of reactive oxygen species by human T-cell leukemia virus type 1 tax correlates with DNA damage and expression of cellular senescence marker. J Virol. 2010;84:5431-7 pubmed publisher
    ..Our data suggest that ROS induction explains Tax-induced cellular DNA damage and cellular senescence. ..
  64. Hieshima K, Nagakubo D, Nakayama T, Shirakawa A, Jin Z, Yoshie O. Tax-inducible production of CC chemokine ligand 22 by human T cell leukemia virus type 1 (HTLV-1)-infected T cells promotes preferential transmission of HTLV-1 to CCR4-expressing CD4+ T cells. J Immunol. 2008;180:931-9 pubmed
    ..CD4+ T cell malignancy which predominantly expresses CCR4 and is etiologically associated with human T cell leukemia virus type 1 (HTLV-1)...
  65. Tang H, Gao W, Chan C, Siu Y, Wong C, Kok K, et al. LKB1 tumor suppressor and salt-inducible kinases negatively regulate human T-cell leukemia virus type 1 transcription. Retrovirology. 2013;10:40 pubmed publisher
    ..Our findings revealed a new function of LKB1 and SIKs as negative regulators of HTLV-1 transcription. Pharmaceutical activation of LKB1 and SIKs might be considered as a new strategy in anti-HTLV-1 and anti-ATL therapy. ..
  66. Chandhasin C, Ducu R, Berkovich E, Kastan M, Marriott S. Human T-cell leukemia virus type 1 tax attenuates the ATM-mediated cellular DNA damage response. J Virol. 2008;82:6952-61 pubmed publisher
    ..Attempts to replicate in the presence of these lesions would result in gradual accumulation of mutations, leading to genome instability and cellular transformation. ..
  67. Kwon H, Ogle L, Benitez B, Bohuslav J, Montano M, Felsher D, et al. Lethal cutaneous disease in transgenic mice conditionally expressing type I human T cell leukemia virus Tax. J Biol Chem. 2005;280:35713-22 pubmed
    ..Of note, this skin disease completely resolved when Tax transgene expression was suppressed by administration of doxycycline, emphasizing the key role played by this viral oncoprotein in the observed pathology...
  68. Gao L, Harhaj E. HSP90 protects the human T-cell leukemia virus type 1 (HTLV-1) tax oncoprotein from proteasomal degradation to support NF-?B activation and HTLV-1 replication. J Virol. 2013;87:13640-54 pubmed publisher
    ..Taken together, our results reveal that Tax is a novel HSP90 client protein and HSP90 inhibitors may exert therapeutic benefits for ATL and HAM/TSP patients...
  69. Ego T, Tanaka Y, Shimotohno K. Interaction of HTLV-1 Tax and methyl-CpG-binding domain 2 positively regulates the gene expression from the hypermethylated LTR. Oncogene. 2005;24:1914-23 pubmed publisher
    ..Our observation provides insight into the epigenetic regulation of gene expression and the diverse mechanisms of transcriptional regulation using methylated promoters...
  70. Wu K, Bottazzi M, de La Fuente C, Deng L, Gitlin S, Maddukuri A, et al. Protein profile of tax-associated complexes. J Biol Chem. 2004;279:495-508 pubmed
  71. Haller K, Wu Y, Derow E, Schmitt I, Jeang K, Grassmann R. Physical interaction of human T-cell leukemia virus type 1 Tax with cyclin-dependent kinase 4 stimulates the phosphorylation of retinoblastoma protein. Mol Cell Biol. 2002;22:3327-38 pubmed
    ..Thus, protein-protein contact between Tax and the components of the cyclin D/CDK complexes provides a further mechanistic explanation for the mitogenic and immortalizing effects of this HTLV-1 oncoprotein. ..
  72. Fryrear K, Durkin S, Gupta S, Tiedebohl J, Semmes O. Dimerization and a novel Tax speckled structure localization signal are required for Tax nuclear localization. J Virol. 2009;83:5339-52 pubmed publisher
    ..Thus, we defined additional domains in Tax specific for nuclear localization and subnuclear targeting. Our results reveal a more complex network for regulation of Tax subcellular localization and subsequent function. ..
  73. Mazurov D, Heidecker G, Derse D. HTLV-1 Gag protein associates with CD82 tetraspanin microdomains at the plasma membrane. Virology. 2006;346:194-204 pubmed publisher
    ..Our data suggest that once at the plasma membrane, HTLV-1 virion components associate with CD82-containing microdomains, which may facilitate the mobilization of nascent virions to sites of intercellular adhesion...
  74. Jeong S, Lu H, Cho W, Park H, Pise Masison C, Brady J. Coactivator-associated arginine methyltransferase 1 enhances transcriptional activity of the human T-cell lymphotropic virus type 1 long terminal repeat through direct interaction with Tax. J Virol. 2006;80:10036-44 pubmed
    ..Together, our data provide evidence that CARM1 enhances Tax transactivation of the HTLV-1 LTR through a direct interaction between CARM1 and Tax and this binding promotes methylation of histone H3 (R2, R17, and R26). ..
  75. Harhaj N, Sun S, Harhaj E. Activation of NF-kappa B by the human T cell leukemia virus type I Tax oncoprotein is associated with ubiquitin-dependent relocalization of I kappa B kinase. J Biol Chem. 2007;282:4185-92 pubmed
    b>Human T cell leukemia virus type 1 (HTLV-1) is the etiological agent of adult T cell leukemia. HTLV-1 encodes a trans-activating protein, Tax, which is largely responsible for the oncogenic properties of the virus...
  76. Hong S, Wang L, Gao X, Kuo Y, Liu B, Merling R, et al. Heptad repeats regulate protein phosphatase 2a recruitment to I-kappaB kinase gamma/NF-kappaB essential modulator and are targeted by human T-lymphotropic virus type 1 tax. J Biol Chem. 2007;282:12119-26 pubmed
    ..Tax-PP2A interaction, however, renders PP2A inactive, thus maintaining Tax-PP2A-IKK in an active state. Finally, CCR2 and LZ possibly inhibit IKK activation by stabilizing the HLX2-CCR2-LZ bundle. ..
  77. Wu X, Sun S. Retroviral oncoprotein Tax deregulates NF-kappaB by activating Tak1 and mediating the physical association of Tak1-IKK. EMBO Rep. 2007;8:510-5 pubmed
    ..These findings show a pathological mechanism of IKK activation by Tax and provide an example for how IKK is persistently activated in cancer cells. ..
  78. Kim Y, Ram rez J, Mick J, Giebler H, Yan J, Nyborg J. Molecular characterization of the Tax-containing HTLV-1 enhancer complex reveals a prominent role for CREB phosphorylation in Tax transactivation. J Biol Chem. 2007;282:18750-7 pubmed publisher
    ..Because pCREB has been implicated in leukemogenesis, enhancement of CREB phosphorylation by the virus may play a role in the etiology of adult T-cell leukemia...
  79. Peloponese J, Kinjo T, Jeang K. Human T-cell leukemia virus type 1 Tax and cellular transformation. Int J Hematol. 2007;86:101-6 pubmed
    ..In this review, we summarize current thinking on how Tax may affect ATL leukemogenesis...
  80. Kfoury Y, Nasr R, Favre Bonvin A, El Sabban M, Renault N, Giron M, et al. Ubiquitylated Tax targets and binds the IKK signalosome at the centrosome. Oncogene. 2008;27:1665-76 pubmed
    ..These observations highlight an unsuspected link between Tax-induced IKK activation and the centrosome...
  81. Wang D, Guo M, Hu H, Zhao Z, Qiu H, Shao H, et al. Human T-cell leukemia virus type 1 oncoprotein tax represses ZNF268 expression through the cAMP-responsive element-binding protein/activating transcription factor pathway. J Biol Chem. 2008;283:16299-308 pubmed publisher
    ..CREB-1 directly at the cAMP-responsive element both in vitro and in vivo. These findings suggest a role for ZNF268 in aberrant T-cell proliferation observed in HTLV-1-associated diseases. ..
  82. Durkin S, Guo X, Fryrear K, Mihaylova V, Gupta S, Belgnaoui S, et al. HTLV-1 Tax oncoprotein subverts the cellular DNA damage response via binding to DNA-dependent protein kinase. J Biol Chem. 2008;283:36311-20 pubmed publisher
    ..We also describe a novel interaction between DNA-PK and Chk2 that requires Tax. We propose that Tax binds to and stabilizes a protein complex with DNA-PK and Chk2, resulting in a saturation of DNA-PK-mediated damage repair response...
  83. Kress A, Kalmer M, Rowan A, Grassmann R, Fleckenstein B. The tumor marker Fascin is strongly induced by the Tax oncoprotein of HTLV-1 through NF-kappaB signals. Blood. 2011;117:3609-12 pubmed publisher
    ..Nuclear factor-?B signals were important for Tax-mediated transcriptional regulation of Fascin in T cells. This suggests that Fascin up-regulation by Tax contributes to the development of HTLV-1-associated pathogenesis...
  84. Blot V, Perugi F, Gay B, Pr vost M, Briant L, Tangy F, et al. Nedd4.1-mediated ubiquitination and subsequent recruitment of Tsg101 ensure HTLV-1 Gag trafficking towards the multivesicular body pathway prior to virus budding. J Cell Sci. 2004;117:2357-67 pubmed publisher
    ..Our findings indicate that Nedd4.1 and Tsg101 act successively in the assembly process of HTLV-1 to ensure proper Gag trafficking through the endocytic pathway up to late endosomes where the late steps of retroviral release occur...
  85. Nakano K, Ando T, Yamagishi M, Yokoyama K, Ishida T, Ohsugi T, et al. Viral interference with host mRNA surveillance, the nonsense-mediated mRNA decay (NMD) pathway, through a new function of HTLV-1 Rex: implications for retroviral replication. Microbes Infect. 2013;15:491-505 pubmed publisher
    ..Thus, we suggest that Rex not only stabilizes viral transcripts, but also perturbs cellular mRNA metabolism and host cell homeostasis via inhibition of NMD...