Histone acetyltransferase (HAT) activity of p300 modulates human T lymphotropic virus type 1 p30{sup II}-mediated repression of LTR transcriptional activity
- Center for Retrovirus Research and Department of Veterinary Biosciences, Ohio State University, Columbus, OH 43210 (United States)
- Ohio State Biochemistry Program, Ohio State University, Columbus, OH 43210 (United States)
- Department of Medicine, Pathology, and Molecular Microbiology, Washington University School of Medicine, St. Louis, MO 63110 (United States)
- Center for Retrovirus Research and Department of Veterinary Biosciences, Ohio State University, Columbus, OH 43210 (United States) and Department of Molecular Virology, Immunology and Medical Genetics, Ohio State University, Columbus, OH 43210 (United States) and Comprehensive Cancer Center, Arthur G. James Cancer Hospital and Solove Research Institute, Ohio State University, Columbus, OH 43210 (United States)
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, p13{sup II} and p30{sup II}, 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 p30{sup II}, 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 p30{sup II} 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 p30{sup II}, 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 p30{sup II} to repress TRE-mediated transcription. Exogenous p300, in a dose-responsive manner, reverses p30{sup II}-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 p30{sup II}-mediated LTR repression. Deacetylation by histone deacetylase-1 (HDAC-1) enhanced p30{sup II}-mediated LTR repression, while inhibition of deacetylation by trichostatin A decreases p30{sup II}-mediated LTR repression. Collectively, our data indicate that HTLV-1 p30{sup II} modulates viral gene expression in a cooperative manner with p300-mediated acetylation.
- OSTI ID:
- 20850573
- Journal Information:
- Virology, Vol. 354, Issue 2; Other Information: DOI: 10.1016/j.virol.2006.07.002; PII: S0042-6822(06)00440-5; Copyright (c) 2006 Elsevier Science B.V., Amsterdam, Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA); ISSN 0042-6822
- Country of Publication:
- United States
- Language:
- English
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