Home LiteratureArticle Details
PMID: 1433511 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Mutational analysis of human T-cell leukemia virus type I Tax: regions necessary for function determined with 47 mutant proteins.

Journal of virology ·Vol. 66 ·No. 12 ·1992-12-00 ·Pages 7183-92

Semmes OJ, Jeang KT

Abstract

We have made 47 mutations that span the length of the human T-cell leukemia virus type I (HTLV-I) Tax open reading frame. Of the 47 mutations, 38 were substitutions of single amino acids, 5 were missense changes in two or more amino acids, and 4 were deletions. A subset of these mutations includes individual changes of all 26 naturally occurring serines to alanines. By assaying each mutant protein separately on the HTLV-I long terminal repeat (LTR) and the human immunodeficiency virus type 1 (HIV-1) LTR in parallel, we were able to identify regions of Tax selectively necessary for each promoter. A small region in the carboxyl terminus, amino acids 315 to 325, was found to be selectively important for activation of the HTLV-I LTR. Three changes at serine 113, serine 160, and serine 258 were found to specifically affect function on the HIV-1 LTR. Surprisingly, we found that the great preponderance of missense changes (32 of 42) in Tax did not affect function.

Related Genes
env gag pol tax
MeSH Terms
Animals Cell Line DNA, Viral/genetics,metabolism Fluorescent Antibody Technique Gene Products, tax/analysis,genetics,metabolism Genes, pX HIV Long Terminal Repeat Human T-lymphotropic virus 1/genetics,metabolism Mutagenesis, Site-Directed Repetitive Sequences, Nucleic Acid Sequence Deletion Subcellular Fractions/metabolism Transcriptional Activation Transfection
Chemicals
DNA, Viral Gene Products, tax
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Semmes O J
Laboratory of Molecular Microbiology, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland 20892.
Jeang K T
References (48)
48 references, click to expand
  1. HTLV-I Tax is a zinc-binding protein: role of zinc in Tax structure and function.
    Virology. 1992 Jun;188(2):754-64 PMID: 1585646
  2. In vitro mutagenesis of the human T-cell leukemia virus types I and II tax genes.
    J Virol. 1989 Mar;63(3):1474-9 PMID: 2783740
  3. Activation of the HIV-1 LTR by T cell mitogens and the trans-activator protein of HTLV-I.
    Science. 1987 Dec 11;238(4833):1575-8 PMID: 2825351
  4. Binding of host-cell factors to DNA sequences in the long terminal repeat of human T-cell leukemia virus type I: implications for viral gene expression.
    Proc Natl Acad Sci U S A. 1988 Mar;85(5):1457-61 PMID: 2830620
  5. Human T-cell leukemia virus types I and II exhibit different DNase I protection patterns.
    J Virol. 1988 Apr;62(4):1339-46 PMID: 2831395
  6. The same inducible nuclear proteins regulates mitogen activation of both the interleukin-2 receptor-alpha gene and type 1 HIV.
    Cell. 1988 Jun 3;53(5):827-36 PMID: 2836068
  7. HTLV-1 transactivator induces interleukin-2 receptor expression through an NF-kappa B-like factor.
    Nature. 1988 Jun 23;333(6175):776-8 PMID: 2838755
  8. Cellular transcription factors and regulation of IL-2 receptor gene expression by HTLV-I tax gene product.
    Science. 1988 Jul 1;241(4861):89-92 PMID: 2838905
  9. Transcriptional activation of homologous viral long terminal repeats by the human immunodeficiency virus type 1 or the human T-cell leukemia virus type I tat proteins occurs in the absence of de novo protein synthesis.
    Proc Natl Acad Sci U S A. 1988 Nov;85(21):8291-5 PMID: 2847157
  10. c-fos promoter trans-activation by the tax1 protein of human T-cell leukemia virus type I.
    Proc Natl Acad Sci U S A. 1988 Nov;85(22):8526-30 PMID: 2847164
  11. Antibodies to human T-lymphotropic virus type-I in patients with tropical spastic paraparesis.
    Lancet. 1985 Aug 24;2(8452):407-10 PMID: 2863442
  12. HTLV-I associated myelopathy, a new clinical entity.
    Lancet. 1986 May 3;1(8488):1031-2 PMID: 2871307
  13. A transcriptional activator protein encoded by the x-lor region of the human T-cell leukemia virus.
    Science. 1985 Jun 21;228(4706):1430-4 PMID: 2990028
  14. The x gene is essential for HTLV replication.
    Science. 1985 Jul 5;229(4708):54-8 PMID: 2990037
  15. The pX protein of HTLV-I is a transcriptional activator of its long terminal repeats.
    Science. 1985 Aug 16;229(4714):675-9 PMID: 2992082
  16. The use of phosphorothioate-modified DNA in restriction enzyme reactions to prepare nicked DNA.
    Nucleic Acids Res. 1985 Dec 20;13(24):8749-64 PMID: 3001649
  17. 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):8359-63 PMID: 3001699
  18. Direct evidence that p40x of human T-cell leukemia virus type I is a trans-acting transcriptional activator.
    EMBO J. 1986 Mar;5(3):561-5 PMID: 3011413
  19. Cis-acting sequences responsible for the transcriptional activation of human T-cell leukemia virus type I constitute a conditional enhancer.
    Proc Natl Acad Sci U S A. 1986 Sep;83(17):6558-62 PMID: 3018737
  20. A single species of pX mRNA of human T-cell leukemia virus type I encodes trans-activator p40x and two other phosphoproteins.
    J Virol. 1986 Nov;60(2):394-9 PMID: 3021974
  21. Requirement of multiple copies of a 21-nucleotide sequence in the U3 regions of human T-cell leukemia virus type I and type II long terminal repeats for trans-acting activation of transcription.
    Proc Natl Acad Sci U S A. 1986 Nov;83(21):8112-6 PMID: 3022280
  22. Induction of interleukin 2 receptor gene expression by p40x encoded by human T-cell leukemia virus type 1.
    EMBO J. 1986 Nov;5(11):2883-8 PMID: 3024966
  23. Evidence for aberrant activation of the interleukin-2 autocrine loop by HTLV-1-encoded p40x and T3/Ti complex triggering.
    Cell. 1987 Jan 30;48(2):343-50 PMID: 3026643
  24. Inhibition of restriction endonuclease Nci I cleavage by phosphorothioate groups and its application to oligonucleotide-directed mutagenesis.
    Nucleic Acids Res. 1986 Dec 22;14(24):9679-98 PMID: 3027659
  25. Regulation of the human interleukin-2 receptor alpha chain promoter: activation of a nonfunctional promoter by the transactivator gene of HTLV-I.
    Cell. 1987 Apr 10;49(1):47-56 PMID: 3030566
  26. Multiple tandemly repeated binding sites for cellular nuclear factor 1 that surround the major immediate-early promoters of simian and human cytomegalovirus.
    J Virol. 1987 May;61(5):1559-70 PMID: 3033283
  27. Stable expression of the tax gene of type I human T-cell leukemia virus in human T cells activates specific cellular genes involved in growth.
    Proc Natl Acad Sci U S A. 1988 Dec;85(24):9733-7 PMID: 3059351
  28. Characterization of cellular factors that interact with the human T-cell leukemia virus type I p40x-responsive 21-base-pair sequence.
    J Virol. 1988 Dec;62(12):4499-509 PMID: 3263510
  29. Transformation of rat cells by DNA of human adenovirus 5.
    Virology. 1973 Aug;54(2):536-9 PMID: 4737663
  30. 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):7415-9 PMID: 6261256
  31. 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):2534-7 PMID: 6326131
  32. Trans-acting transcriptional activation of the long terminal repeat of human T lymphotropic viruses in infected cells.
    Science. 1984 Jul 27;225(4660):381-5 PMID: 6330891
  33. Recombinant genomes which express chloramphenicol acetyltransferase in mammalian cells.
    Mol Cell Biol. 1982 Sep;2(9):1044-51 PMID: 6960240
  34. Complex formation of human T-cell leukemia virus type I p40tax transactivator with cellular polypeptides.
    J Virol. 1992 Feb;66(2):1040-9 PMID: 1731090
  35. Characterization of a novel nuclear localization signal in the HTLV-I tax transactivator protein.
    Virology. 1992 Mar;187(1):316-20 PMID: 1736534
  36. Interaction of the human T-cell lymphotrophic virus type I (HTLV-I) transcriptional activator Tax with cellular factors that bind specifically to the 21-base-pair repeats in the HTLV-I enhancer.
    Proc Natl Acad Sci U S A. 1991 Dec 15;88(24):11445-9 PMID: 1763059
  37. Induction of the HTLV-I LTR by Jun occurs through the Tax-responsive 21-bp elements.
    Virology. 1991 Mar;181(1):218-27 PMID: 1899734
  38. Binding of the HTLV-I Tax1 transactivator to the inducible 21 bp enhancer is mediated by the cellular factor HEB1.
    EMBO J. 1991 Dec;10(12):3795-803 PMID: 1935901
  39. Transdominant human T-cell lymphotropic virus type I TAX1 mutant that fails to localize to the nucleus.
    J Virol. 1991 May;65(5):2612-21 PMID: 2016773
  40. trans-activation of the HIV-1 LTR by the HIV-1 Tat and HTLV-I Tax proteins is mediated by different cis-acting sequences.
    Virology. 1991 Jun;182(2):874-8 PMID: 2024503
  41. PROSITE: a dictionary of sites and patterns in proteins.
    Nucleic Acids Res. 1991 Apr 25;19 Suppl:2241-5 PMID: 2041810
  42. The indirect association of human T-cell leukemia virus tax protein with DNA results in transcriptional activation.
    J Virol. 1991 Aug;65(8):4525-8 PMID: 2072462
  43. Cellular factors involved in transcription and Tax-mediated trans-activation directed by the TGACGT motifs in human T-cell leukemia virus type I promoter.
    J Biol Chem. 1990 Nov 25;265(33):20285-92 PMID: 2243093
  44. Identification of HTLV-I tax trans-activator mutants exhibiting novel transcriptional phenotypes.
    Genes Dev. 1990 Nov;4(11):1875-85 PMID: 2276622
  45. HTLV-I trans-activator protein, tax, is a trans-repressor of the human beta-polymerase gene.
    Science. 1990 Mar 2;247(4946):1082-4 PMID: 2309119
  46. Tax1 induction of the HTLV-I 21 bp enhancer requires cooperation between two cellular DNA-binding proteins.
    EMBO J. 1990 Mar;9(3):957-64 PMID: 2311587
  47. Trans-activation of the human immunodeficiency virus long terminal repeat sequence by DNA viruses.
    Proc Natl Acad Sci U S A. 1986 Dec;83(24):9759-63 PMID: 2432602
  48. Purification and characterization of multiple nuclear factors that bind to the TAX-inducible enhancer within the human T-cell leukemia virus type 1 long terminal repeat.
    Mol Cell Biol. 1989 Apr;9(4):1733-45 PMID: 2786141
Article Info
Journal
Journal of virology
Abbr.
J Virol
ISSN
0022-538X
DOI
10.1128/JVI.66.12.7183-7192.1992
Published
1992-12-00
Pages
7183-92
Language
English
Region
United States
NLM ID
0113724
PMCID
PMC240413
Subset
IM
External Links
PubMed source DOI: 10.1128/JVI.66.12.7183-7192.1992 PMC Full Text View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: [email protected]

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2