Histone acetyltransferase (HAT) activity of p300 modulates human T lymphotropic virus type 1 p30II-mediated repression of LTR transcriptional activity
| Autor: | Antara Datta, Michael Dale Lairmore, Lee Ratner, Bindhu Michael, Amrithraj M. Nair, Hajime Hiraragi |
|---|---|
| Rok vydání: | 2006 |
| Předmět: |
Gene Expression Regulation
Viral Transcription Genetic T-Lymphocytes viruses Retroviridae Proteins Replication p300 Cell Cycle Proteins P300-CBP Transcription Factors Article Viral Proteins Transcription (biology) Virology Humans Histone acetyltransferase activity p300-CBP Transcription Factors CREB-binding protein Cyclic AMP Response Element-Binding Protein Transcription factor Psychological repression Histone Acetyltransferases Human T-lymphotropic virus 1 Retrovirus biology Terminal Repeat Sequences Acetylation Accessory Protein Histone acetyltransferase Provirus CREB-Binding Protein Molecular biology HTLV-1 Trans-Activators biology.protein Lymphocyte HeLa Cells Transcription Factors |
| Zdroj: | Virology. 354:225-239 |
| ISSN: | 0042-6822 |
| DOI: | 10.1016/j.virol.2006.07.002 |
| Popis: | Human T-lymphotropic virus type-1 (HTLV-1) is a deltaretrovirus that causes adult T cell leukemia/lymphoma, and is implicated in a variety of lymphocyte-mediated inflammatory disorders. HTLV-1 provirus has regulatory and accessory genes in four pX open reading frames. HTLV-1 pX ORF-II encodes two proteins, p13II and p30II, which are incompletely defined in virus replication or pathogenesis. We have demonstrated that pX ORF-II mutations block virus replication in vivo and that ORF-II encoded p30II, a nuclear-localizing protein that binds with CREB-binding protein (CBP)/p300, represses CREB and Tax responsive element (TRE)-mediated transcription. Herein, we have identified p30II motifs important for p300 binding and in regulating TRE-mediated transcription in the absence and presence of HTLV-1 provirus. Within amino acids 100–179 of p30II, a region important for repression of LTR-mediated transcription, we identified a single lysine residue at amino acid 106 (K3) that significantly modulates the ability of p30II to repress TRE-mediated transcription. Exogenous p300, in a dose-responsive manner, reverses p30II-dependent repression of TRE-mediated transcription, in the absence or presence of the provirus, In contrast to wild type p300, p300 HAT mutants (defective in histone acetyltransferase activity) only partially rescued p30II-mediated LTR repression. Deacetylation by histone deacetylase-1 (HDAC-1) enhanced p30II-mediated LTR repression, while inhibition of deacetylation by trichostatin A decreases p30II-mediated LTR repression. Collectively, our data indicate that HTLV-1 p30II modulates viral gene expression in a cooperative manner with p300-mediated acetylation. |
| Databáze: | OpenAIRE |
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