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PMID: 12438606 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

The complementary strand of the human T-cell leukemia virus type 1 RNA genome encodes a bZIP transcription factor that down-regulates viral transcription.

Journal of virology ·Vol. 76 ·No. 24 ·2002-12-00 ·Pages 12813-22

Gaudray G, Gachon F, Basbous J, Biard-Piechaczyk M, Devaux C, Mesnard JM

Abstract

The RNA genome of the human T-cell leukemia virus type 1 (HTLV-1) codes for proteins involved in infectivity, replication, and transformation. We report in this study the characterization of a novel viral protein encoded by the complementary strand of the HTLV-1 RNA genome. This protein, designated HBZ (for HTLV-1 bZIP factor), contains a N-terminal transcriptional activation domain and a leucine zipper motif in its C terminus. We show here that HBZ is able to interact with the bZIP transcription factor CREB-2 (also called ATF-4), known to activate the HTLV-1 transcription by recruiting the viral trans-activator Tax on the Tax-responsive elements (TxREs). However, we demonstrate that the HBZ/CREB-2 heterodimers are no more able to bind to the TxRE and cyclic AMP response element sites. Taking these findings together, the functional inactivation of CREB-2 by HBZ is suggested to contribute to regulation of the HTLV-1 transcription. Moreover, the characterization of a minus-strand gene protein encoded by HTLV-1 has never been reported until now.

MeSH Terms
Activating Transcription Factor 4 Amino Acid Sequence Animals Basic-Leucine Zipper Transcription Factors COS Cells DNA-Binding Proteins/chemistry,genetics Down-Regulation G-Box Binding Factors Gene Expression Regulation, Viral Human T-lymphotropic virus 1/genetics Molecular Sequence Data RNA, Complementary/genetics RNA, Viral/genetics Transcription Factors/chemistry,genetics,metabolism Transcription, Genetic
Chemicals
Basic-Leucine Zipper Transcription Factors DNA-Binding Proteins G-Box Binding Factors RNA, Complementary RNA, Viral Transcription Factors Activating Transcription Factor 4
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Gaudray Gilles
Laboratoire Infections Rétrovirales et Signalisation Cellulaire, CNRS/UM I UMR 5121, Institut de Biologie, 4 Boulevard Henri IV, 34060 Montpellier, France.
Gachon Frederic
Basbous Jihane
Biard-Piechaczyk Martine
Devaux Christian
Mesnard Jean-Michel
References (37)
37 references, click to expand
  1. Molecular interactions involved in the transactivation of the human T-cell leukemia virus type 1 promoter mediated by Tax and CREB-2 (ATF-4).
    Mol Cell Biol. 2000 May;20(10):3470-81 PMID: 10779337
  2. Crystal structure of the CCAAT box/enhancer-binding protein beta activating transcription factor-4 basic leucine zipper heterodimer in the absence of DNA.
    J Biol Chem. 2001 Jan 5;276(1):505-13 PMID: 11018027
  3. Molecular cloning of a novel human I-mfa domain-containing protein that differently regulates human T-cell leukemia virus type I and HIV-1 expression.
    J Biol Chem. 2000 Feb 18;275(7):4848-57 PMID: 10671520
  4. CREB-2, a cellular CRE-dependent transcription repressor, functions in association with Tax as an activator of the human T-cell leukemia virus type 1 promoter.
    J Virol. 1998 Oct;72(10):8332-7 PMID: 9733879
  5. The cAMP response element binding protein-2 (CREB-2) can interact with the C/EBP-homologous protein (CHOP).
    FEBS Lett. 2001 Jul 27;502(1-2):57-62 PMID: 11478948
  6. Activation of HTLV-I transcription in the presence of Tax is independent of the acetylation of CREB-2 (ATF-4).
    Virology. 2002 Aug 1;299(2):271-8 PMID: 12202230
  7. 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
  8. Transcription factor ATF cDNA clones: an extensive family of leucine zipper proteins able to selectively form DNA-binding heterodimers.
    Genes Dev. 1989 Dec;3(12B):2083-90 PMID: 2516827
  9. HTLV-I Tax protein stimulation of DNA binding of bZIP proteins by enhancing dimerization.
    Science. 1993 Oct 15;262(5132):395-9 PMID: 8211160
  10. Expression status of Tax protein in human T-cell leukemia virus type 1-transformed MT4 cells: recall of MT4 cells distributed by the NIH AIDS Research and Reference Reagent Program.
    J Virol. 1997 Sep;71(9):6277-8 PMID: 9261343
  11. Isolation of cDNAs for DNA-binding proteins which specifically bind to a tax-responsive enhancer element in the long terminal repeat of human T-cell leukemia virus type I.
    J Virol. 1991 Mar;65(3):1420-6 PMID: 1847461
  12. HTLV-I Tax self-association in optimal trans-activation function.
    Nucleic Acids Res. 1997 Jan 15;25(2):379-87 PMID: 9016568
  13. The Ick protein tyrosine kinase is not involved in antibody-mediated CD4 (CDR3-loop) signal transduction that inhibits HIV-1 transcription.
    Eur J Immunol. 1998 May;28(5):1445-57 PMID: 9603449
  14. Mechanisms of Tax Regulation of Human T Cell Leukemia Virus Type I Gene Expression.
    J Biomed Sci. 1995 Jan;2(1):17-29 PMID: 11725037
  15. Quantitative studies of the effect of HTLV-I Tax protein on CREB protein--DNA binding.
    Nucleic Acids Res. 1994 Aug 11;22(15):3194-201 PMID: 8065935
  16. Human T-cell leukemia virus minus strand transcription in infected T-cells.
    Biochem Biophys Res Commun. 1989 Sep 15;163(2):1006-13 PMID: 2476979
  17. Human T-cell lymphotropic virus type I (HTLV-I) transcriptional activator, Tax, enhances CREB binding to HTLV-I 21-base-pair repeats by protein-protein interaction.
    Proc Natl Acad Sci U S A. 1992 Aug 1;89(15):7070-4 PMID: 1386673
  18. Post-transcriptional regulator (rex) of HTLV-1 initiates expression of viral structural proteins but suppresses expression of regulatory proteins.
    EMBO J. 1988 Feb;7(2):519-23 PMID: 2835230
  19. Identification of activating transcription factor 4 (ATF4) as an Nrf2-interacting protein. Implication for heme oxygenase-1 gene regulation.
    J Biol Chem. 2001 Jun 15;276(24):20858-65 PMID: 11274184
  20. The trans-activator tax of human T-cell leukemia virus type 1 (HTLV-1) interacts with cAMP-responsive element (CRE) binding and CRE modulator proteins that bind to the 21-base-pair enhancer of HTLV-1.
    Proc Natl Acad Sci U S A. 1993 Jan 15;90(2):610-4 PMID: 8421695
  21. Transforming potential of the herpesvirus oncoprotein MEQ: morphological transformation, serum-independent growth, and inhibition of apoptosis.
    J Virol. 1998 Jan;72(1):388-95 PMID: 9420237
  22. Nuclear targeting of cAMP response element binding protein 2 (CREB2).
    Eur J Cell Biol. 1999 Sep;78(9):642-9 PMID: 10535306
  23. Transactivation by the human T-cell leukemia virus Tax protein is mediated through enhanced binding of activating transcription factor-2 (ATF-2) ATF-2 response and cAMP element-binding protein (CREB).
    J Biol Chem. 1993 Oct 5;268(28):21225-31 PMID: 8407959
  24. Control of cAMP-regulated enhancers by the viral transactivator Tax through CREB and the co-activator CBP.
    Nature. 1996 Apr 18;380(6575):642-6 PMID: 8602268
  25. A transcriptional enhancer sequence of HTLV-I is responsible for trans-activation mediated by p40 chi HTLV-I.
    EMBO J. 1986 Apr;5(4):713-8 PMID: 3011423
  26. Nuclear translocation and DNA recognition signals colocalized within the bZIP domain of cyclic adenosine 3',5'-monophosphate response element-binding protein CREB.
    Mol Endocrinol. 1991 Oct;5(10):1431-8 PMID: 1837841
  27. p300-mediated tax transactivation from recombinant chromatin: histone tail deletion mimics coactivator function.
    Mol Cell Biol. 2002 Jan;22(1):127-37 PMID: 11739728
  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. Molecular cloning of human CREB-2: an ATF/CREB transcription factor that can negatively regulate transcription from the cAMP response element.
    Proc Natl Acad Sci U S A. 1992 Jun 1;89(11):4820-4 PMID: 1534408
  30. Transcriptional regulation by cyclic AMP.
    Annu Rev Biochem. 1997;66:807-22 PMID: 9242925
  31. Complex formation between CREB and Tax enhances the binding affinity of CREB for the human T-cell leukemia virus type 1 21-base-pair repeats.
    Mol Cell Biol. 1996 Jun;16(6):3156-68 PMID: 8649426
  32. Distinct roles of Jun : Fos and Jun : ATF dimers in oncogenesis.
    Oncogene. 2001 Apr 30;20(19):2453-64 PMID: 11402340
  33. Biological role of the CCAAT/enhancer-binding protein family of transcription factors.
    J Biol Chem. 1998 Oct 30;273(44):28545-8 PMID: 9786841
  34. Marek disease virus encodes a basic-leucine zipper gene resembling the fos/jun oncogenes that is highly expressed in lymphoblastoid tumors.
    Proc Natl Acad Sci U S A. 1992 May 1;89(9):4042-6 PMID: 1315048
  35. Functional interaction of the HTLV-1 transactivator Tax with activating transcription factor-4 (ATF4).
    Oncogene. 1997 Jun 12;14(23):2785-92 PMID: 9190894
  36. A natural antisense RNA derived from the HIV-1 env gene encodes a protein which is recognized by circulating antibodies of HIV+ individuals.
    Virology. 1995 Jan 10;206(1):196-202 PMID: 7831774
  37. Transformation of intact yeast cells treated with alkali cations.
    J Bacteriol. 1983 Jan;153(1):163-8 PMID: 6336730
Article Info
Journal
Journal of virology
Abbr.
J Virol
ISSN
0022-538X
DOI
10.1128/jvi.76.24.12813-12822.2002
Published
2002-12-00
Pages
12813-22
Language
English
Region
United States
NLM ID
0113724
PMCID
PMC136662
Subset
IM
External Links
PubMed source DOI: 10.1128/jvi.76.24.12813-12822.2002 PMC Full Text View journal details
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