The HBZ factor of human T-cell leukemia virus type I dimerizes with transcription factors JunB and c-Jun and modulates their transcriptional activity.
The human T-cell leukemia virus type I (HTLV-I)-encoded Tax protein activates transcription from the viral promoter via association with the cellular basic leucine zipper factor cAMP-response element-binding protein-2. Tax is also able to induce cellular transformation of T lymphocytes probably by modulating transcriptional activity of cellular factors, including nuclear factor-kappaB, E2F, activator protein-1 (AP-1), and p53. Recently, we characterized in HTLV-I-infected cells the presence of a novel viral protein, HBZ, encoded by the complementary strand of the HTLV-I RNA genome (Gaudray, G., Gachon, F., Basbous, J., Biard-Piechaczyk, M., Devaux, C., and Mesnard, J.-M. (2002) J. Virol. 76, 12813-12822). HBZ is a nuclear basic leucine zipper protein that down-regulates Tax-dependent viral transcription by inhibiting the binding of cAMP-response element-binding protein-2 to the HTLV-I promoter. In searching for other cellular targets of HBZ, we identified two members of the Jun family, JunB and c-Jun. Co-immunoprecipitation and cellular colocalization confirmed that HBZ interacts in vivo with JunB and c-Jun. When transiently introduced into CEM cells with a reporter gene containing the AP-1 site from the collagenase promoter, HBZ suppressed transactivation by c-Jun. On the other hand, the combination of HBZ with Jun-B had higher transcriptional activity than JunB alone. Consistent with the structure of its basic domain, we demonstrate that HBZ decreases the DNA-binding activity of c-Jun and JunB. Last, we show that c-Jun is no longer capable of activating the basal expression of the HTLV-I promoter in the presence of HBZ in vivo. Our results support the hypothesis that HBZ could be a negative modulator of the Tax effect by controlling Tax expression at the transcriptional level and by attenuating activation of AP-1 by Tax.
Basbous
Jihane
J
Laboratoire Infections Rétrovirales et Signalisation Cellulaire, CNRS/Université Montpellier I, Unité Mixte de Recherche 5121/Institut Fédératif de Recherche 122, Institut de Biologie, 4 Boulevard Henri IV, 34960 Montpellier Cedex 2, France.
Arpin
Charlotte
C
Gaudray
Gilles
G
Piechaczyk
Marc
M
Devaux
Christian
C
Mesnard
Jean-Michel
JM
D000818:Animals; D050976:Basic-Leucine Zipper Transcription Factors; D001665:Binding Sites; D001710:Biotin / Q000378:metabolism; D015153:Blotting, Western; D019556:COS Cells; D017364:Collagenases / Q000235:genetics; D018076:DNA, Complementary / Q000378:metabolism; D019281:Dimerization; D015536:Down-Regulation; D016356:Gene Products, tax / Q000096:biosynthesis; D017930:Genes, Reporter; D016679:Genome, Viral; D005982:Glutathione Transferase / Q000378:metabolism; D006367:HeLa Cells; D015368:Human T-lymphotropic virus 1 / Q000378:metabolism*; D006801:Humans; D016350:Leucine Zippers; D008156:Luciferases / Q000378:metabolism; D008856:Microscopy, Fluorescence; D011233:Precipitin Tests; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D016755:Proto-Oncogene Proteins c-jun / Q000378:metabolism*; D012313:RNA / Q000378:metabolism; D012191:Retroviridae Proteins; D019809:Streptavidin / Q000494:pharmacology; D013997:Time Factors; D018808:Transcription Factor AP-1 / Q000378:metabolism; D014157:Transcription Factors / Q000737:chemistry* / Q000502:physiology*; D014158:Transcription, Genetic; D015533:Transcriptional Activation; D014162:Transfection; D020798:Two-Hybrid System Techniques; D014764:Viral Proteins / Q000737:chemistry* / Q000502:physiology*; D001616:beta-Galactosidase / Q000378:metabolism
D050976:Basic-Leucine Zipper Transcription Factors; D018076:DNA, Complementary; D016356:Gene Products, tax; C479751:HBZ protein, human T-cell leukemia virus type I; D016755:Proto-Oncogene Proteins c-jun; D012191:Retroviridae Proteins; D018808:Transcription Factor AP-1; D014157:Transcription Factors; D014764:Viral Proteins; D012313:RNA; D001710:Biotin; D019809:Streptavidin; D008156:Luciferases; D005982:Glutathione Transferase; D001616:beta-Galactosidase; D017364:Collagenases