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PMID: 2536828 Published · ppublish English Journal Article

Mutational analysis of the conserved basic domain of human immunodeficiency virus tat protein.

Journal of virology ·Vol. 63 ·No. 3 ·1989-03-00 ·Pages 1181-7

Hauber J, Malim MH, Cullen BR

Abstract

The tat trans-activators encoded by the known strains of primate immunodeficiency virus share a conserved, highly basic protein domain. Mutagenesis of this sequence in the tat gene of human immunodeficiency virus type 1 is shown here to reduce, but not eliminate, the trans-activation of human immunodeficiency virus type 1-specific gene expression. The degree of inhibition is shown to vary in a dose-dependent manner and is most marked at low levels of tat expression. Multiple mutations of the basic domain of tat were found to impair both the in vivo stability and the nuclear localization of the tat protein. It is proposed that this protein domain serves to efficiently target the tat gene product to its appropriate site or substrate within the nucleus of expressing cells.

MeSH Terms
Cell Compartmentation DNA Mutational Analysis Fluorescent Antibody Technique Gene Expression Regulation Gene Products, tat HIV/genetics,metabolism Nuclear Proteins/genetics Precipitin Tests Retroviridae Proteins/genetics,metabolism Structure-Activity Relationship Transcription Factors/genetics tat Gene Products, Human Immunodeficiency Virus
Chemicals
Gene Products, tat Nuclear Proteins Retroviridae Proteins Transcription Factors tat Gene Products, Human Immunodeficiency Virus
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Hauber J
Howard Hughes Medical Institute, Duke University Medical Center, Durham, North Carolina 27710.
Malim M H
Cullen B R
References (36)
36 references, click to expand
  1. Trans-activation of human immunodeficiency virus gene expression is mediated by nuclear events.
    Proc Natl Acad Sci U S A. 1987 Sep;84(18):6364-8 PMID: 3476953
  2. Missense mutations in an infectious human immunodeficiency viral genome: functional mapping of tat and identification of the rev splice acceptor.
    Proc Natl Acad Sci U S A. 1988 Dec;85(23):9224-8 PMID: 3194421
  3. The nuclear migration signal of Xenopus laevis nucleoplasmin.
    EMBO J. 1987 Sep;6(9):2617-25 PMID: 3119324
  4. Anti-termination of transcription within the long terminal repeat of HIV-1 by tat gene product.
    Nature. 1987 Dec 3-9;330(6147):489-93 PMID: 2825027
  5. Two signals mediate hormone-dependent nuclear localization of the glucocorticoid receptor.
    EMBO J. 1987 Nov;6(11):3333-40 PMID: 3123217
  6. Induction of nuclear transport with a synthetic peptide homologous to the SV40 T antigen transport signal.
    Cell. 1986 Aug 15;46(4):575-82 PMID: 3015419
  7. HTLV-III expression and production involve complex regulation at the levels of splicing and translation of viral RNA.
    Cell. 1986 Sep 12;46(6):807-17 PMID: 3638988
  8. Trans-activation of human immunodeficiency virus occurs via a bimodal mechanism.
    Cell. 1986 Sep 26;46(7):973-82 PMID: 3530501
  9. Mutational analysis of the trans-activation-responsive region of the human immunodeficiency virus type I long terminal repeat.
    J Virol. 1988 Mar;62(3):673-9 PMID: 2828663
  10. Structural and functional characterization of human immunodeficiency virus tat protein.
    J Virol. 1989 Jan;63(1):1-8 PMID: 2535718
  11. Targeting of E. coli beta-galactosidase to the nucleus in yeast.
    Cell. 1984 Apr;36(4):1057-65 PMID: 6323016
  12. A short amino acid sequence able to specify nuclear location.
    Cell. 1984 Dec;39(3 Pt 2):499-509 PMID: 6096007
  13. The location of cis-acting regulatory sequences in the human T cell lymphotropic virus type III (HTLV-III/LAV) long terminal repeat.
    Cell. 1985 Jul;41(3):813-23 PMID: 2988790
  14. Trans-activator gene of human T-lymphotropic virus type III (HTLV-III).
    Science. 1985 Jul 5;229(4708):69-73 PMID: 2990040
  15. Location of the trans-activating region on the genome of human T-cell lymphotropic virus type III.
    Science. 1985 Jul 5;229(4708):74-7 PMID: 2990041
  16. Nuclear location signals in polyoma virus large-T.
    Cell. 1986 Jan 17;44(1):77-85 PMID: 3000623
  17. The rapid generation of oligonucleotide-directed mutations at high frequency using phosphorothioate-modified DNA.
    Nucleic Acids Res. 1985 Dec 20;13(24):8765-85 PMID: 3001650
  18. The trans-activator gene of the human T cell lymphotropic virus type III is required for replication.
    Cell. 1986 Mar 28;44(6):941-7 PMID: 2420471
  19. The trans-activator gene of HTLV-III is essential for virus replication.
    Nature. 1986 Mar 27-Apr 2;320(6060):367-71 PMID: 3007995
  20. AIDS retrovirus (ARV-2) clone replicates in transfected human and animal fibroblasts.
    Science. 1986 May 23;232(4753):998-1001 PMID: 3010461
  21. Expression and characterization of the trans-activator of HTLV-III/LAV virus.
    Science. 1986 Nov 21;234(4779):988-92 PMID: 3490693
  22. Elevated levels of mRNA can account for the trans-activation of human immunodeficiency virus.
    Proc Natl Acad Sci U S A. 1986 Dec;83(24):9734-8 PMID: 3025848
  23. Regulation of mRNA accumulation by a human immunodeficiency virus trans-activator protein.
    Cell. 1987 Feb 27;48(4):691-701 PMID: 3643816
  24. Genome organization and transactivation of the human immunodeficiency virus type 2.
    Nature. 1987 Apr 16-22;326(6114):662-9 PMID: 3031510
  25. The genome organization of STLV-3 is similar to that of the AIDS virus except for a truncated transmembrane protein.
    Cell. 1987 May 8;49(3):307-19 PMID: 3646094
  26. New human and simian HIV-related retroviruses possess functional transactivator (tat) gene.
    Nature. 1987 Aug 6-12;328(6130):548-50 PMID: 3039372
  27. Subnuclear localization of the trans-activating protein of human T-cell leukemia virus type I.
    J Virol. 1988 Mar;62(3):680-6 PMID: 2828664
  28. Amino acid sequences that determine the nuclear localization of yeast histone 2B.
    Mol Cell Biol. 1987 Nov;7(11):4048-57 PMID: 3123916
  29. Tat protein from human immunodeficiency virus forms a metal-linked dimer.
    Science. 1988 Apr 1;240(4848):70-3 PMID: 2832944
  30. Sequence of simian immunodeficiency virus from African green monkey, a new member of the HIV/SIV group.
    Nature. 1988 Jun 2;333(6172):457-61 PMID: 3374586
  31. Two nuclear location signals in the influenza virus NS1 nonstructural protein.
    J Virol. 1988 Aug;62(8):3020-6 PMID: 2969057
  32. Immunodeficiency virus rev trans-activator modulates the expression of the viral regulatory genes.
    Nature. 1988 Sep 8;335(6186):181-3 PMID: 3412474
  33. Secreted placental alkaline phosphatase: a powerful new quantitative indicator of gene expression in eukaryotic cells.
    Gene. 1988 Jun 15;66(1):1-10 PMID: 3417148
  34. Sequence requirements for nucleolar localization of human T cell leukemia virus type I pX protein, which regulates viral RNA processing.
    Cell. 1988 Oct 21;55(2):197-209 PMID: 3048703
  35. Functional domains required for tat-induced transcriptional activation of the HIV-1 long terminal repeat.
    EMBO J. 1988 Oct;7(10):3143-7 PMID: 3181132
  36. Use of eukaryotic expression technology in the functional analysis of cloned genes.
    Methods Enzymol. 1987;152:684-704 PMID: 3657593
Article Info
Journal
Journal of virology
Abbr.
J Virol
ISSN
0022-538X
Published
1989-03-00
Pages
1181-7
Language
English
Region
United States
NLM ID
0113724
PMCID
PMC247813
Subset
IM
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