Document Detail

Direct interactions of Kaposi's sarcoma-associated herpesvirus/human herpesvirus 8 ORF50/Rta protein with the cellular protein octamer-1 and DNA are critical for specifying transactivation of a delayed-early promoter and stimulating viral reactivation.
MedLine Citation:
PMID:  17537858     Owner:  NLM     Status:  MEDLINE    
The Kaposi's sarcoma-associated herpesvirus (KSHV) delayed-early K-bZIP promoter contains an ORF50/Rta binding site whose sequence is conserved with the ORF57 promoter. Mutation of the site in the full-length K-bZIP promoter reduced Rta-mediated transactivation by greater than 80%. The K-bZIP element contains an octamer (Oct) binding site that overlaps the Rta site and is well conserved with Oct elements found in the immediate-early promoters of herpes simplex virus type 1(HSV-1). The cellular protein Oct-1, but not Oct-2, binds to the K-bZIP element in a sequence-specific fashion in vitro and in vivo and stimulates Rta binding to the promoter DNA. The coexpression of Oct-1 enhances Rta-mediated transactivation of the wild type but not the mutant K-bZIP promoter, and Oct-1 and Rta proteins bind to each other directly in vitro. Mutations of Rta within an amino acid sequence conserved with HSV-1 virion protein 16 eliminate Rta's interactions with Oct-1 and K-bZIP promoter DNA but not RBP-Jk. The binding of Rta to both Oct-1 and DNA contributes to the transactivation of the K-bZIP promoter and viral reactivation, and Rta mutants deficient for both interactions are completely debilitated. Our data suggest that the Rta/Oct-1 interaction is essential for optimal KSHV reactivation. Transfections of mouse embryo fibroblasts and an endothelial cell line suggest cell-specific differences in the requirement for Oct-1 or RBP-Jk in Rta-mediated transactivation of the K-bZIP promoter. We propose a model in which Rta transactivation of the promoter is specified by the combination of DNA binding and interactions with several cellular DNA binding proteins including Oct-1.
Kyla Driscoll Carroll; Farah Khadim; Sophia Spadavecchia; Diana Palmeri; David M Lukac
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2007-05-30
Journal Detail:
Title:  Journal of virology     Volume:  81     ISSN:  0022-538X     ISO Abbreviation:  J. Virol.     Publication Date:  2007 Aug 
Date Detail:
Created Date:  2007-07-26     Completed Date:  2007-09-13     Revised Date:  2013-06-06    
Medline Journal Info:
Nlm Unique ID:  0113724     Medline TA:  J Virol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  8451-67     Citation Subset:  IM    
Department of Microbiology and Molecular Genetics, University of Medicine and Dentistry of New Jersey/New Jersey Medical School, 225 Warren Street, Newark, NJ 07103, USA.
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MeSH Terms
Amino Acid Motifs
Amino Acid Sequence
Base Sequence
Basic-Leucine Zipper Transcription Factors / genetics*
Binding Sites
Cell Line
Cells, Cultured
DNA / metabolism
Fibroblasts / metabolism
Gene Expression Regulation, Viral*
Herpesvirus 8, Human / genetics,  physiology*
Immediate-Early Proteins / analysis,  genetics,  metabolism*
Immunoglobulin J Recombination Signal Sequence-Binding Protein / metabolism
Molecular Sequence Data
Nuclear Proteins / metabolism
Octamer Transcription Factor-1 / analysis,  genetics,  metabolism*
Promoter Regions, Genetic
Protein Interaction Mapping
Repressor Proteins / genetics*
Response Elements
Trans-Activators / analysis,  genetics,  metabolism*
Transcriptional Activation*
Viral Proteins / analysis,  genetics*,  metabolism*
Virus Activation / genetics*
Reg. No./Substance:
0/Basic-Leucine Zipper Transcription Factors; 0/Immediate-Early Proteins; 0/Immunoglobulin J Recombination Signal Sequence-Binding Protein; 0/K8 protein, Human herpesvirus 8; 0/Nuclear Proteins; 0/Octamer Transcription Factor-1; 0/Repressor Proteins; 0/Rta protein, Human herpesvirus 8; 0/Trans-Activators; 0/Viral Proteins; 9007-49-2/DNA

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