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EMBO J. Mar 1986; 5(3): 561–565.
PMCID: PMC1166799

Direct evidence that p40x of human T-cell leukemia virus type I is a trans-acting transcriptional activator.

Abstract

Human T-cell leukemia virus type I has a unique sequence, pX, between the env gene and the 3'LTR (long terminal repeat). This sequence codes for p40x, which was proposed to trans-activate transcription from the LTR. Recently, we identified novel pX proteins coded by frame III, which mostly overlaps frame IV (x-lor, coding for p40x), in a region also overlapped by frame II. To determine which product is responsible for the trans-acting function, we constructed an active provirus clone, pMTPX, that contained a genomic fragment of the env, pX and 3'LTR, and introduced site-directed mutations into the active site. The effects of various deletions and point mutations that distinguished each of the overlapping open reading frames (ORFs), II, III and IV, on trans-activation of pLTR-CAT were treated by co-transfection assays. The results showed that only mutations which affected p40x expression resulted in loss of activity for transcriptional activation. These findings clearly indicate that p40x coded by frame IV is responsible for the transcriptional activation of the LTR. This conclusion was confirmed by studies on expression of cDNA of pX mRNA.

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Selected References

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  • Kiyokawa T, Seiki M, Imagawa K, Shimizu F, Yoshida M. Identification of a protein (p40x) encoded by a unique sequence pX of human T-cell leukemia virus type I. Gann. 1984 Sep;75(9):747–751. [PubMed]
  • Kiyokawa T, Seiki M, Iwashita S, Imagawa K, Shimizu F, Yoshida M. p27x-III and p21x-III, proteins encoded by the pX sequence of human T-cell leukemia virus type I. Proc Natl Acad Sci U S A. 1985 Dec;82(24):8359–8363. [PMC free article] [PubMed]
  • Kiyokawa T, Kawaguchi T, Seiki M, Yoshida M. Association of the pX gene product of human T-cell leukemia virus type-I with nucleus. Virology. 1985 Dec;147(2):462–465. [PubMed]
  • Lee TH, Coligan JE, Sodroski JG, Haseltine WA, Salahuddin SZ, Wong-Staal F, Gallo RC, Essex M. Antigens encoded by the 3'-terminal region of human T-cell leukemia virus: evidence for a functional gene. Science. 1984 Oct 5;226(4670):57–61. [PubMed]
  • Miwa M, Shimotohno K, Hoshino H, Fujino M, Sugimura T. Detection of pX proteins in human T-cell leukemia virus (HTLV)-infected cells by using antibody against peptide deduced from sequences of X-IV DNA of HTLV-I and Xc DNA of HTLV-II proviruses. Gann. 1984 Sep;75(9):752–755. [PubMed]
  • Poiesz BJ, Ruscetti FW, Gazdar AF, Bunn PA, Minna JD, Gallo RC. Detection and isolation of type C retrovirus particles from fresh and cultured lymphocytes of a patient with cutaneous T-cell lymphoma. Proc Natl Acad Sci U S A. 1980 Dec;77(12):7415–7419. [PMC free article] [PubMed]
  • Sagata N, Yasunaga T, Tsuzuku-Kawamura J, Ohishi K, Ogawa Y, Ikawa Y. Complete nucleotide sequence of the genome of bovine leukemia virus: its evolutionary relationship to other retroviruses. Proc Natl Acad Sci U S A. 1985 Feb;82(3):677–681. [PMC free article] [PubMed]
  • Seiki M, Hattori S, Hirayama Y, Yoshida M. Human adult T-cell leukemia virus: complete nucleotide sequence of the provirus genome integrated in leukemia cell DNA. Proc Natl Acad Sci U S A. 1983 Jun;80(12):3618–3622. [PMC free article] [PubMed]
  • Seiki M, Eddy R, Shows TB, Yoshida M. Nonspecific integration of the HTLV provirus genome into adult T-cell leukaemia cells. Nature. 1984 Jun 14;309(5969):640–642. [PubMed]
  • Seiki M, Hikikoshi A, Taniguchi T, Yoshida M. Expression of the pX gene of HTLV-I: general splicing mechanism in the HTLV family. Science. 1985 Jun 28;228(4707):1532–1534. [PubMed]
  • Seiki M, Inoue J, Takeda T, Hikikoshi A, Sato M, Yoshida M. The p40x of human T-cell leukemia virus type I is a trans-acting activator of viral gene transcription. Jpn J Cancer Res. 1985 Dec;76(12):1127–1131. [PubMed]
  • Shimotohno K, Wachsman W, Takahashi Y, Golde DW, Miwa M, Sugimura T, Chen IS. Nucleotide sequence of the 3' region of an infectious human T-cell leukemia virus type II genome. Proc Natl Acad Sci U S A. 1984 Nov;81(21):6657–6661. [PMC free article] [PubMed]
  • Slamon DJ, Shimotohno K, Cline MJ, Golde DW, Chen IS. Identification of the putative transforming protein of the human T-cell leukemia viruses HTLV-I and HTLV-II. Science. 1984 Oct 5;226(4670):61–65. [PubMed]
  • Slamon DJ, Press MF, Souza LM, Murdock DC, Cline MJ, Golde DW, Gasson JC, Chen IS. Studies of the putative transforming protein of the type I human T-cell leukemia virus. Science. 1985 Jun 21;228(4706):1427–1430. [PubMed]
  • Sodroski JG, Rosen CA, Haseltine WA. Trans-acting transcriptional activation of the long terminal repeat of human T lymphotropic viruses in infected cells. Science. 1984 Jul 27;225(4660):381–385. [PubMed]
  • Sodroski J, Rosen C, Goh WC, Haseltine W. A transcriptional activator protein encoded by the x-lor region of the human T-cell leukemia virus. Science. 1985 Jun 21;228(4706):1430–1434. [PubMed]
  • Wachsman W, Golde DW, Temple PA, Orr EC, Clark SC, Chen IS. HTLV x-gene product: requirement for the env methionine initiation codon. Science. 1985 Jun 28;228(4707):1534–1537. [PubMed]
  • Watanabe T, Seiki M, Tsujimoto H, Miyoshi I, Hayami M, Yoshida M. Sequence homology of the simian retrovirus genome with human T-cell leukemia virus type I. Virology. 1985 Jul 15;144(1):59–65. [PubMed]
  • Wong-Staal F, Hahn B, Manzari V, Colombini S, Franchini G, Gelmann EP, Gallo RC. A survey of human leukaemias for sequences of a human retrovirus. Nature. 1983 Apr 14;302(5909):626–628. [PubMed]
  • Yoshida M, Miyoshi I, Hinuma Y. Isolation and characterization of retrovirus from cell lines of human adult T-cell leukemia and its implication in the disease. Proc Natl Acad Sci U S A. 1982 Mar;79(6):2031–2035. [PMC free article] [PubMed]
  • Yoshida M, Seiki M, Yamaguchi K, Takatsuki K. Monoclonal integration of human T-cell leukemia provirus in all primary tumors of adult T-cell leukemia suggests causative role of human T-cell leukemia virus in the disease. Proc Natl Acad Sci U S A. 1984 Apr;81(8):2534–2537. [PMC free article] [PubMed]
  • Banerji J, Olson L, Schaffner W. A lymphocyte-specific cellular enhancer is located downstream of the joining region in immunoglobulin heavy chain genes. Cell. 1983 Jul;33(3):729–740. [PubMed]
  • Breathnach R, Chambon P. Organization and expression of eucaryotic split genes coding for proteins. Annu Rev Biochem. 1981;50:349–383. [PubMed]
  • Brinster RL, Chen HY, Trumbauer M, Senear AW, Warren R, Palmiter RD. Somatic expression of herpes thymidine kinase in mice following injection of a fusion gene into eggs. Cell. 1981 Nov;27(1 Pt 2):223–231. [PubMed]
  • Chen IS, Slamon DJ, Rosenblatt JD, Shah NP, Quan SG, Wachsman W. The x gene is essential for HTLV replication. Science. 1985 Jul 5;229(4708):54–58. [PubMed]
  • Clapham P, Nagy K, Cheingsong-Popov R, Exley M, Weiss RA. Productive infection and cell-free transmission of human T-cell leukemia virus in a nonlymphoid cell line. Science. 1983 Dec 9;222(4628):1125–1127. [PubMed]
  • Felber BK, Paskalis H, Kleinman-Ewing C, Wong-Staal F, Pavlakis GN. The pX protein of HTLV-I is a transcriptional activator of its long terminal repeats. Science. 1985 Aug 16;229(4714):675–679. [PubMed]
  • Fujisawa J, Seiki M, Kiyokawa T, Yoshida M. Functional activation of the long terminal repeat of human T-cell leukemia virus type I by a trans-acting factor. Proc Natl Acad Sci U S A. 1985 Apr;82(8):2277–2281. [PMC free article] [PubMed]
  • Goh WC, Sodroski J, Rosen C, Essex M, Haseltine WA. Subcellular localization of the product of the long open reading frame of human T-cell leukemia virus type I. Science. 1985 Mar 8;227(4691):1227–1228. [PubMed]
  • Graham FL, van der Eb AJ. A new technique for the assay of infectivity of human adenovirus 5 DNA. Virology. 1973 Apr;52(2):456–467. [PubMed]
  • Haseltine WA, Sodroski J, Patarca R, Briggs D, Perkins D, Wong-Staal F. Structure of 3' terminal region of type II human T lymphotropic virus: evidence for new coding region. Science. 1984 Jul 27;225(4660):419–421. [PubMed]
  • Hinuma Y, Nagata K, Hanaoka M, Nakai M, Matsumoto T, Kinoshita KI, Shirakawa S, Miyoshi I. Adult T-cell leukemia: antigen in an ATL cell line and detection of antibodies to the antigen in human sera. Proc Natl Acad Sci U S A. 1981 Oct;78(10):6476–6480. [PMC free article] [PubMed]
  • Hollenberg SM, Lai JS, Weickmann JL, Date T. Primer-directed mutagenesis of linearized plasmids. Anal Biochem. 1984 Dec;143(2):341–349. [PubMed]
  • Kingston RE, Baldwin AS, Sharp PA. Transcription control by oncogenes. Cell. 1985 May;41(1):3–5. [PubMed]

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