px genes


Summary: DNA sequences that form the coding region for at least three proteins which regulate the expression of HUMAN T-LYMPHOTROPIC VIRUS 1 and HUMAN T-LYMPHOTROPIC VIRUS 2. The proteins are p21(x), p27(rex), and p40(tax). The tax (trans-activator x) and rex (regulator x) genes are part of pX but are in overlapping reading frames. X was the original designation for the sequences or region (at that time of unknown function) in the long open reading frame (lor) which is now called pX.

Top Publications

  1. Younis I, Khair L, Dundr M, Lairmore M, Franchini G, Green P. Repression of human T-cell leukemia virus type 1 and type 2 replication by a viral mRNA-encoded posttranscriptional regulator. J Virol. 2004;78:11077-83 pubmed
    ..These data are consistent with the critical role of these proteins in viral persistence and pathogenesis in animal models of HTLV-1 and HTLV-2 infection...
  2. Nicot C, Dundr M, Johnson J, Fullen J, Alonzo N, Fukumoto R, et al. HTLV-1-encoded p30II is a post-transcriptional negative regulator of viral replication. Nat Med. 2004;10:197-201 pubmed
    ..Because Tex and Rex are positive regulators of viral gene expression, their inhibition by p30(II) reduces virion production. p30(II) inhibits virus expression by reducing Tax and Rex protein expression. ..
  3. Taylor G, Matsuoka M. Natural history of adult T-cell leukemia/lymphoma and approaches to therapy. Oncogene. 2005;24:6047-57 pubmed
    ..To avoid further unnecessary patient suffering and to identify optimal therapy as rapidly as possible, large randomized, controlled trials encompassing multicenter, international collaborations will be necessary. ..
  4. Yoshida M. Discovery of HTLV-1, the first human retrovirus, its unique regulatory mechanisms, and insights into pathogenesis. Oncogene. 2005;24:5931-7 pubmed
    ..The unique regulatory mechanisms for the viral regulation with Tax and Rex, etiology of ATL and possible leukemogenic mechanism with Tax are also discussed briefly...
  5. Ratner L. Pathogenesis and treatment of human T-cell leukemia virus infection. Immunol Res. 2005;32:217-23 pubmed
    ..Translational clinical studies of chemotherapy, interferon-alpha, and nucleoside reverse transcriptase inhibitors have also assisted in identifying the pathogenic features of ATLL. ..
  6. Neuveut C, Jeang K. Cell cycle dysregulation by HTLV-I: role of the tax oncoprotein. Front Biosci. 2002;7:d157-63 pubmed
    ..Here, we review extant data on how Tax targets cyclins, inhibitors of cyclin dependent kinase, as well as cellular sentries for DNA-damage. ..
  7. Mulloy J, Kislyakova T, Cereseto A, Casareto L, LoMonico A, Fullen J, et al. Human T-cell lymphotropic/leukemia virus type 1 Tax abrogates p53-induced cell cycle arrest and apoptosis through its CREB/ATF functional domain. J Virol. 1998;72:8852-60 pubmed
    ..The suppression of p53 activity by Tax could be important in T-cell immortalization induced by HTLV-1. ..
  8. Pique C, Ureta Vidal A, Gessain A, Chancerel B, Gout O, Tamouza R, et al. Evidence for the chronic in vivo production of human T cell leukemia virus type I Rof and Tof proteins from cytotoxic T lymphocytes directed against viral peptides. J Exp Med. 2000;191:567-72 pubmed
    ..These findings indicate that the HTLV-I pX-I and pX-II proteins are chronically synthesized in vivo, and are targets of the natural immune response to the virus. ..
  9. Derse D, Mikovits J, Ruscetti F. X-I and X-II open reading frames of HTLV-I are not required for virus replication or for immortalization of primary T-cells in vitro. Virology. 1997;237:123-8 pubmed
    ..Thus, ORFs X-I and X-II are not essential for virus infectivity, replication, gene expression, or T-cell immortalization in vitro. ..

More Information


  1. Koralnik I, Fullen J, Franchini G. The p12I, p13II, and p30II proteins encoded by human T-cell leukemia/lymphotropic virus type I open reading frames I and II are localized in three different cellular compartments. J Virol. 1993;67:2360-6 pubmed
    ..The defined localization of these proteins in specific cellular compartments warrants further study of their function. ..
  2. Furukawa Y, Kubota R, Tara M, Izumo S, Osame M. Existence of escape mutant in HTLV-I tax during the development of adult T-cell leukemia. Blood. 2001;97:987-93 pubmed
  3. Zendri E, Pilotti E, Perez M, Turci M, Pinelli S, Ronzi P, et al. The HTLV tax-like sequences in cutaneous T-cell lymphoma patients. J Invest Dermatol. 2008;128:489-92 pubmed
  4. Murata K, Yamada Y. The state of the art in the pathogenesis of ATL and new potential targets associated with HTLV-1 and ATL. Int Rev Immunol. 2007;26:249-68 pubmed
    ..Here we review the state of the art regarding our understanding of ATL leukemogenesis and new potential molecular targets in ATL therapy. ..
  5. Miyatake Y, Ikeda H, Ishizu A, Baba T, Ichihashi T, Suzuki A, et al. Role of neuronal interferon-gamma in the development of myelopathy in rats infected with human T-cell leukemia virus type 1. Am J Pathol. 2006;169:189-99 pubmed
    ..We suggest that the failure of spinal cord neurons to produce IFN-gamma through the IL-12 pathway is involved in the development of HAM rat disease. ..
  6. Gabet A, Gessain A, Wattel E. High simian T-cell leukemia virus type 1 proviral loads combined with genetic stability as a result of cell-associated provirus replication in naturally infected, asymptomatic monkeys. Int J Cancer. 2003;107:74-83 pubmed
  7. Iwakura Y, Itagaki K, Ishitsuka C, Yamasaki Y, Matsuzawa A, Yonehara S, et al. The development of autoimmune inflammatory arthropathy in mice transgenic for the human T cell leukemia virus type-1 env-pX region is not dependent on H-2 haplotypes and modified by the expression levels of Fas antigen. J Immunol. 1998;161:6592-8 pubmed
    ..These observations suggest that aberration of Fas-mediated apoptosis of peripheral lymphocytes, rather than negative selection in the thymus, is involved in the development of autoimmune arthropathy in pX-Tg mice. ..
  8. Fujii M, Niinuma A, Higuchi M. [HTLV-1, 2]. Nihon Rinsho. 2003;61 Suppl 3:503-7 pubmed
  9. Segurado A, Malaque C, Sumita L, Pannuti C, Lal R. Laboratory characterization of human T cell lymphotropic virus types 1 (HTLV-1) and 2 (HTLV-2) infections in blood donors from Sao Paulo, Brazil. Am J Trop Med Hyg. 1997;57:142-8 pubmed
    ..All seroindeterminate donors were also negative by PCR. HTLV-1 could be isolated in cocultures from 10 of 18 infected donors. ..
  10. Boris Lawrie K, Altanerova V, Altaner C, Kucerova L, Temin H. In vivo study of genetically simplified bovine leukemia virus derivatives that lack tax and rex. J Virol. 1997;71:1514-20 pubmed
    ..These viruses will be useful tools in comparative studies with BLV to evaluate the role of tax and rex in maintenance of virus load and in disease outcome...
  11. Hirata M. [Higher expression levels of alternatively spliced pX mRNA in human T lymphotropic virus type I (HTLV-I) asymptomatic carriers positive for antibodies to p40tax protein]. Fukuoka Igaku Zasshi. 1996;87:23-34 pubmed
    ..Our observations may explain previous finding that the carriers rate is higher in the offspring of anti-p40tax positive mothers than those of anti-p40tax negative mothers. ..
  12. Nomura M, Ohashi T, Nishikawa K, Nishitsuji H, Kurihara K, Hasegawa A, et al. Repression of tax expression is associated both with resistance of human T-cell leukemia virus type 1-infected T cells to killing by tax-specific cytotoxic T lymphocytes and with impaired tumorigenicity in a rat model. J Virol. 2004;78:3827-36 pubmed
    ..Our results provide insights into the mechanisms how the host immune system can survey and inhibit the growth of HTLV-1-infected cells during the long latent period before the onset of ATL. ..
  13. McGirr K, Buehuring G. Tax & rex: overlapping genes of the Deltaretrovirus group. Virus Genes. 2006;32:229-39 pubmed
  14. Davidson F, Lycett C, Jarvis L, Kerr D, Lumley S, Petrik J, et al. Detection of HTLV-I and -II in Scottish blood donor samples and archive donations. Vox Sang. 2006;91:231-6 pubmed
    ..HTLV PCR confirmation will provide additional useful information for donor medical staff for counselling donors. ..
  15. Mitra Kaushik S, Harding J, Hess J, Ratner L. Effects of the proteasome inhibitor PS-341 on tumor growth in HTLV-1 Tax transgenic mice and Tax tumor transplants. Blood. 2004;104:802-9 pubmed
    ..TUNEL staining indicated that PS-341 treatment sensitizes Tax tumors to DNA fragmentation. ..
  16. Datta A, Silverman L, Phipps A, Hiraragi H, Ratner L, Lairmore M. Human T-lymphotropic virus type-1 p30 alters cell cycle G2 regulation of T lymphocytes to enhance cell survival. Retrovirology. 2007;4:49 pubmed
  17. Beilke M, Traina Dorge V, Sirois M, Bhuiyan A, Murphy E, Walls J, et al. Relationship between human T lymphotropic virus (HTLV) type 1/2 viral burden and clinical and treatment parameters among patients with HIV type 1 and HTLV-1/2 coinfection. Clin Infect Dis. 2007;44:1229-34 pubmed
    ..Highly active antiretroviral therapy may be of limited value in controlling virus expression of HTLV-1/2 in patients with HIV-HTLV-1/2 coinfection. ..
  18. 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...
  19. Miyano Kurosaki N, Koyanagi Y, Mizuguchi M, Ohki S, Makino K, Yamamoto N. Inhibition of HTLV-I induction and virus-induced syncytia formation by oligodeoxynucleotides. Virus Genes. 1996;12:205-17 pubmed
  20. Das S, Gitschier J. Identification of a TXREB pseudogene (TXREBP) located between the genes for p55 (MPP1) and G6PD on Xq28. Genomics. 1994;21:275-8 pubmed
    ..Further analysis showed that the gene is expressed in a variety of human tissues and that the pseudogene is located between the genes for the proteins p55 and G6PD. ..
  21. Sharma V, Lorey S. Autocrine role of macrophage inflammatory protein-1 beta in human T-cell lymphotropic virus type-I tax-transfected Jurkat T-cells. Biochem Biophys Res Commun. 2001;287:910-3 pubmed
    ..These results, coupled with our earlier observations, demonstrate the influence that extracellular Tax protein might have on modulating host chemokines for proliferation and transformation of uninfected cells. ..
  22. Belec L, Georges Courbot M, Georges A, Mohamed A, Londos Gagliardi D, Hallouin M, et al. Cervicovaginal synthesis of IgG antibodies to the immunodominant 175-199 domain of the surface glycoprotein gp46 of human T-cell leukemia virus type I. J Med Virol. 1996;50:42-9 pubmed
    ..Since anti-gp46/175-Pro-199 antibodies usually support reactivities to neutralizing domains, their presence could be relevant for limiting HTLV-I transmission via cervicovaginal secretions. ..
  23. Zhang J, Yamada O, Kawagishi K, Araki H, Yamaoka S, Hattori T, et al. Human T-cell leukemia virus type 1 Tax modulates interferon-alpha signal transduction through competitive usage of the coactivator CBP/p300. Virology. 2008;379:306-13 pubmed publisher
    ..This study suggests that Tax may prevent IFN-alpha from exerting its antiviral, antiproliferative and proapoptotic effects, thereby contributing to persistent viral infection and HTLV-1-associated oncogenesis...
  24. Barsov E, Andersen H, Coalter V, Carrington M, Lifson J, Ott D. Capture of antigen-specific T lymphocytes from human blood by selective immortalization to establish long-term T-cell lines maintaining primary cell characteristics. Immunol Lett. 2006;105:26-37 pubmed
    ..This approach provides a convenient, reproducible means for generating a stable, continuously renewable source of antigen-specific T lymphocytes for a variety of studies of T cell biology. ..
  25. Furukawa Y, Tara M, Izumo S, Arimura K, Osame M. HTLV-I viral escape and host genetic changes in the development of adult T cell leukemia. Int J Cancer. 2006;118:381-7 pubmed
    ..Our findings suggest that CTL escape mutation can occur at an early stage of ATL development, and that certain host genetic changes favor the development of the aggressive form of ATL. ..
  26. Zucker Franklin D, Pancake B, Friedman Kien A. Cutaneous disease resembling mycosis fungoides in HIV-infected patients whose skin and blood cells also harbor proviral HTLV type I. AIDS Res Hum Retroviruses. 1994;10:1173-7 pubmed
    ..Dual infections could result in clinical manifestations and evolution of disease not anticipated in patients who harbor only one of these retroviruses. ..
  27. Pichler K, Jeang K. Remembering Ralph Grassmann (1957-2008). Retrovirology. 2008;5:71 pubmed publisher
  28. Fukami Kobayashi K, Tateno Y. Robustness of maximum likelihood tree estimation against different patterns of base substitutions. J Mol Evol. 1991;32:79-91 pubmed
    ..The results are in accordance with those from the simulation study, showing that Jukes and Cantor's model is as useful as a more complicated one for making inferences about molecular phylogeny of the viruses. ..
  29. Kashima S, Alcantara L, Takayanagui O, Cunha M, Castro B, Pombo de Oliveira M, et al. Distribution of human T cell lymphotropic virus type 1 (HTLV-1) subtypes in Brazil: genetic characterization of LTR and tax region. AIDS Res Hum Retroviruses. 2006;22:953-9 pubmed
    ..These changes were not correlated with a specific clinical status of the patients and could be a molecular characteristic of the HTLV-1 strains that circulate in Brazil. ..
  30. Miyazato P, Yasunaga J, Taniguchi Y, Koyanagi Y, Mitsuya H, Matsuoka M. De novo human T-cell leukemia virus type 1 infection of human lymphocytes in NOD-SCID, common gamma-chain knockout mice. J Virol. 2006;80:10683-91 pubmed
    ..In this study, we demonstrated that the human PBMC-NOG mouse model should be a useful tool in studying the early stages of primary HTLV-1 infection. ..
  31. Jeang K. HTLV-1 and adult T-cell leukemia: insights into viral transformation of cells 30 years after virus discovery. J Formos Med Assoc. 2010;109:688-93 pubmed publisher
    ..This review discusses recent insights into the role of the HTLV-1 Tax oncoprotein in cellular proliferation and the abrogation of cellular checkpoints that lead to disease progression. ..
  32. Nose H, Kubota R, Seth N, Goon P, Tanaka Y, Izumo S, et al. Ex vivo analysis of human T lymphotropic virus type 1-specific CD4+ cells by use of a major histocompatibility complex class II tetramer composed of a neurological disease-susceptibility allele and its immunodominant peptide. J Infect Dis. 2007;196:1761-72 pubmed publisher
  33. Tsuji T. [Malignant transformation of epithelial thymoma developed in HTLV-I pX transgenic rat by heterotopic transplantation and its molecular analysis]. Hokkaido Igaku Zasshi. 2003;78:503-13 pubmed
  34. Kikuchi K, Ikeda H, Tsuchikawa T, Tsuji T, Tanaka S, Fugo K, et al. A novel animal model of thymic tumour: development of epithelial thymoma in transgenic rats carrying human T lymphocyte virus type I pX gene. Int J Exp Pathol. 2002;83:247-55 pubmed
    ..The transgenic rat model described here is suitable as a model for analysing tumorigenesis in epithelial thymoma occurring in humans. ..
  35. Mori N, Morishita M, Tsukazaki T, Giam C, Kumatori A, Tanaka Y, et al. Human T-cell leukemia virus type I oncoprotein Tax represses Smad-dependent transforming growth factor beta signaling through interaction with CREB-binding protein/p300. Blood. 2001;97:2137-44 pubmed
    ..The novel function of Tax as a repressor of TGF-beta signaling may contribute to HTLV-I leukemogenesis. (Blood. 2001;97:2137-2144) ..
  36. Fang J, Kushida S, Feng R, Tanaka M, Kawamura T, Abe H, et al. Transmission of human T-cell leukemia virus type 1 to mice. J Virol. 1998;72:3952-7 pubmed
    ..HTLV-1 provirus was found in the T-cell fraction of the mouse spleen. These results indicate that mice can be infected by HTLV-1 and could serve as an animal model for the study of HTLV-1 infection and its pathogenesis in vivo. ..
  37. Okayama A, Korber B, Chen Y, Allan J, Lee T, Shioiri S, et al. Unusual pattern of antibodies to human T-cell leukemia virus type-I in family members of adult T-cell leukemia patients. Blood. 1991;78:3323-9 pubmed
    ..DNA samples from lymphocytes of four individuals with antibody reactivity only to HTLV-I tax were tested in polymerase chain reaction experiments; no HTLV-I or -II DNA was detected...
  38. Villanueva R, Iglesias A, Camelo S, Sanin L, Gray S, Dangond F. Histone deacetylase 3 represses HTLV-1 tax transcription. Oncol Rep. 2006;16:581-5 pubmed
    ..Immunoprecipitation studies revealed that Tax co-exists in a complex containing both histone deacetylase 1 (HDAC1) and 3 (HDAC3). Our results suggest that HDACs may actively participate in the repression of HTLV-1 Tax transcription. ..
  39. Kawaki H, Kubota S, Minato M, Moritani N, Hattori T, Hanagata H, et al. Novel enzyme-linked immunosorbent assay systems for the quantitative analysis of connective tissue growth factor (CTGF/Hcs24/CCN2): detection of HTLV-I tax-induced CTGF from a human carcinoma cell line. DNA Cell Biol. 2003;22:641-8 pubmed
    ..Since CTGF is actually processed into subfragments, and functional assignment of each module is of interest, these systems are expected to contribute to the progress of CTGF investigations. ..
  40. Imada K, Takaori Kondo A, Akagi T, Shimotohno K, Sugamura K, Hattori T, et al. Tumorigenicity of human T-cell leukemia virus type I-infected cell lines in severe combined immunodeficient mice and characterization of the cells proliferating in vivo. Blood. 1995;86:2350-7 pubmed
  41. Yasunaga J, Matsuoka M. Human T-cell leukemia virus type I induces adult T-cell leukemia: from clinical aspects to molecular mechanisms. Cancer Control. 2007;14:133-40 pubmed
    ..ATL is a neoplastic disease of CD4-positive T lymphocytes that is characterized by pleomorphic tumor cells with hypersegmented nuclei, termed "flower cells." The mechanisms of leukemogenesis have not been fully clarified...
  42. Tsuji T, Ikeda H, Tsuchikawa T, Kikuchi K, Baba T, Ishizu A, et al. Malignant transformation of thymoma in recipient rats by heterotopic thymus transplantation from HTLV-I transgenic rats. Lab Invest. 2005;85:851-61 pubmed
    ..Our model described here is a useful unique model for in vivo malignant transformation. ..
  43. Tosswill J, Taylor G, Clewley J, Weber J. Quantification of proviral DNA load in human T-cell leukaemia virus type I infections. J Virol Methods. 1998;75:21-6 pubmed
    ..0 copies in patients with HAM and 1.55 copies in initially asymptomatic carriers. The assay was used to test for low proviral load in subjects who may have HTLV-I infection, and to monitor response to therapy. ..
  44. Westendorp M, Li Weber M, Frank R, Krammer P. Human immunodeficiency virus type 1 Tat upregulates interleukin-2 secretion in activated T cells. J Virol. 1994;68:4177-85 pubmed
    ..Furthermore, it might contribute to the hypergammaglobulinemia or, together with other cytokines found to be dysregulated, the T-helper cell dysfunctions observed in AIDS patients. ..
  45. Ng P, Iha H, Iwanaga Y, Bittner M, Chen Y, Jiang Y, et al. Genome-wide expression changes induced by HTLV-1 Tax: evidence for MLK-3 mixed lineage kinase involvement in Tax-mediated NF-kappaB activation. Oncogene. 2001;20:4484-96 pubmed
    ..Functionally, we provide evidence that one of these genes, the mixed-lineage kinase MLK-3, is involved in Tax-mediated NF-kappa-B signaling. Our current results provide additional insights into Tax-mediated signaling. ..
  46. Matsuoka M. [Mechanism of oncogenesis by human T-cell leukemia virus type 1]. Gan To Kagaku Ryoho. 2010;37:10-3 pubmed
    ..Thus, HBZ modulates cellular signal pathways in addition to promoted proliferation. These findings indicate that HBZ is an essential viral gene for oncogenesis by HTLV-1. ..
  47. Yamagata T, Nishida J, Tanaka S, Sakai R, Mitani K, Yoshida M, et al. A novel interferon regulatory factor family transcription factor, ICSAT/Pip/LSIRF, that negatively regulates the activity of interferon-regulated genes. Mol Cell Biol. 1996;16:1283-94 pubmed
    ..These results suggest that a novel mechanism of gene regulation by "differential repression" is used by multiple members of repressor proteins with different repressive effects on the IFN-responsive genes. ..
  48. Barbeau B, Mesnard J. Does the HBZ gene represent a new potential target for the treatment of adult T-cell leukemia?. Int Rev Immunol. 2007;26:283-304 pubmed
    ..How could this new discovery be translated into possible new avenues for the prevention or treatment of ATL? ..
  49. Slavcev R, Hayes S. Stationary phase-like properties of the bacteriophage lambda Rex exclusion phenotype. Mol Genet Genomics. 2003;269:40-8 pubmed
    ..Our observations support the hypothesis that the Rex system can cause a stationary-phase-like response that protects the host against infection by T4 rII. ..
  50. Ishizu A, Tsuji T, Abe A, Saito S, Takahashi T, Ikeda H, et al. Transduction of dominant negative ATF-1 suppresses the pX gene expression in joint fibroblastic cells derived from HTLV-I transgenic rats. Exp Mol Pathol. 2003;74:309-13 pubmed
    ..Expression of the pX gene in cells transduced with ATF-1DN was lower than that in cells with control transfection. A possible application of ATF-1DN to suppress viral gene expression in HTLV-I infected cells can be considered. ..
  51. Takeda S, Maeda M, Morikawa S, Taniguchi Y, Yasunaga J, Nosaka K, et al. Genetic and epigenetic inactivation of tax gene in adult T-cell leukemia cells. Int J Cancer. 2004;109:559-67 pubmed