Human T-cell leukemia virus type 1 (HTLV-1) bZIP protein interacts with the cellular transcription factor CREB to inhibit HTLV-1 transcription
Autor: | Isabelle Lemasson, Sabine Thébault, Benoit Barbeau, Matthew R. Lewis, Jennifer K. Nyborg, Patrick Hivin, Nicholas Polakowski, Jean-Michel Mesnard, Marie-Hélène Cavanagh |
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Přispěvatelé: | East Carolina University [Greenville] (ECU), University of North Carolina System (UNC), Colorado State University [Fort Collins] (CSU), Institut de Recherche en Infectiologie de Montpellier (IRIM), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Centre de Recherche en Infectiologie, CHU de Québec, Infections rétrovirales et signalisation cellulaire (IRSC), Université Montpellier 1 (UM1)-Centre National de la Recherche Scientifique (CNRS), Département des Sciences Biologiques [Montréal], Université du Québec à Montréal = University of Québec in Montréal (UQAM), ARC |
Jazyk: | angličtina |
Rok vydání: | 2007 |
Předmět: |
Transcription
Genetic viruses Activating transcription factor rétrovirus MESH: Down-Regulation Transactivation MESH: Protein Structure Tertiary MESH: Gene Expression Regulation Viral 0302 clinical medicine Retrovirus Transcription (biology) Gene expression MESH: Gene Products tax MESH: Animals Cyclic AMP Response Element-Binding Protein Promoter Regions Genetic Genetics 0303 health sciences Human T-lymphotropic virus 1 biology bZIP domain Gene Products tax 3. Good health Cell biology Genome Replication and Regulation of Viral Gene Expression MESH: Promoter Regions (Genetics) Basic-Leucine Zipper Transcription Factors [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology MESH: Cyclic AMP Response Element-Binding Protein Gene Expression Regulation Viral Immunology Down-Regulation [SDV.CAN]Life Sciences [q-bio]/Cancer MESH: Basic-Leucine Zipper Transcription Factors CREB Microbiology Cell Line ATF/CREB 03 medical and health sciences Viral Proteins Virology Animals Humans leucémie 030304 developmental biology MESH: Human T-lymphotropic virus 1 MESH: Humans MESH: Transcription Genetic biology.organism_classification MESH: Viral Proteins Protein Structure Tertiary MESH: Cell Line HTLV-1 Insect Science biology.protein 030215 immunology |
Zdroj: | Journal of Virology Journal of Virology, American Society for Microbiology, 2007, 81 (4), pp.1543-53. ⟨10.1128/JVI.00480-06⟩ |
ISSN: | 0022-538X 1098-5514 |
DOI: | 10.1128/JVI.00480-06⟩ |
Popis: | The complex human T-cell leukemia virus type 1 (HTLV-1) retrovirus encodes several proteins that are unique to the virus within its 3′-end region. Among them, the viral transactivator Tax and posttranscriptional regulator Rex are well characterized, and both positively regulate HTLV-1 viral expression. Less is known about the other regulatory proteins encoded in this region of the provirus, including the recently discovered HBZ protein. HBZ has been shown to negatively regulate basal and Tax-dependent HTLV-1 transcription through its ability to interact with specific basic-leucine zipper (bZIP) proteins. In the present study, we found that HBZ reduces HTLV-1 transcription and virion production. We then characterized the interaction between HBZ and the cellular transcription factor CREB. CREB plays a critical role in Tax-mediated HTLV-1 transcription by forming a complex with Tax that binds to viral cyclic AMP-response elements (CREs) located within the viral promoter. We found that HBZ and CREB interact in vivo and directly in vitro, and this interaction occurs through the bZIP domain of each protein. We also found that CREM-Ia and ATF-1, which share significant homology in their bZIP domains with the bZIP domain of CREB, interact with HBZ-bZIP. The interaction between CREB and HBZ prevents CREB binding to the viral CRE elements in vitro and in vivo, suggesting that the reduction in HTLV-1 transcription by HBZ is partly due to the loss of CREB at the promoter. We also found that HBZ displaces CREB from a cellular CRE, suggesting that HBZ may deregulate CREB-dependent cellular gene expression. |
Databáze: | OpenAIRE |
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