Epstein-Barr virus EBNA-3C is targeted to and regulates expression from the bidirectional LMP-1/2B promoter.
| Title: | Epstein-Barr virus EBNA-3C is targeted to and regulates expression from the bidirectional LMP-1/2B promoter. |
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| Authors: | Jiménez-Ramírez C; Department of Biochemistry, MS 340, 332 North Lauderdale Street, Memphis, TN 38105, USA.; Brooks AJ; Forshell LP; Yakimchuk K; Zhao B; Fulgham TZ; Sample CE |
| Source: | Journal of virology [J Virol] 2006 Nov; Vol. 80 (22), pp. 11200-8. Date of Electronic Publication: 2006 Sep 06. |
| Publication Type: | Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't |
| Language: | English |
| Journal Info: | Publisher: American Society For Microbiology Country of Publication: United States NLM ID: 0113724 Publication Model: Print-Electronic Cited Medium: Print ISSN: 0022-538X (Print) Linking ISSN: 0022538X NLM ISO Abbreviation: J Virol Subsets: MEDLINE |
| Imprint Name(s): | Publication: Washington Dc : American Society For Microbiology; Original Publication: Baltimore, American Society for Microbiology. |
| MeSH Terms: | Gene Expression Regulation, Viral* ; Promoter Regions, Genetic*; Antigens, Viral/*metabolism ; Herpesvirus 4, Human/*physiology ; Viral Matrix Proteins/*genetics; Antigens, Viral/physiology ; DNA, Viral/metabolism ; DNA-Binding Proteins/analysis ; Epstein-Barr Virus Nuclear Antigens/analysis ; Proto-Oncogene Proteins/analysis ; RNA, Viral/analysis ; Trans-Activators/analysis ; Transcription Factors/analysis ; Viral Matrix Proteins/biosynthesis ; Viral Proteins/analysis ; Cell Line, Tumor ; Chromatin Immunoprecipitation ; Electrophoresis, Polyacrylamide Gel ; Humans ; Immunoblotting ; Reverse Transcriptase Polymerase Chain Reaction ; Proto-Oncogene Protein Spi-1 |
| Abstract: | Epstein-Barr virus (EBV) nuclear antigen 3C (EBNA-3C) is essential for EBV-mediated immortalization of human B lymphocytes and regulates both the cell cycle and transcription. Transient reporter gene assays have implicated a pivotal role for EBNA-3C in the regulation of transcription of the majority of latency-associated genes expressed during the EBV growth program, including the viral oncoprotein LMP-1. To examine the regulation of latency gene expression by EBNA-3C, we generated an EBV-positive cell line that inducibly expresses EBNA-3C. This cell line allowed us to examine expression from the endogenous latency gene promoters in the context of an actual latent infection and the presence of other EBNA proteins, in particular EBNA-2, which is presumed to coregulate transcription with EBNA-3C. EBNA-3C induced the expression of both LMP-1 and LMP-2B mRNAs from the bidirectional LMP-1/LMP-2B promoter. In contrast, no effect was seen on expression from the common EBNA promoter Cp, which is responsive to EBNA-3C in reporter assays. Activation of LMP expression was not the consequence of increases in EBNA-2, PU.1 or Spi-B transcription factors, all of which are believed to be critical for activation of LMP-1. Chromatin immunoprecipitation assays furthermore indicated that EBNA-3C is present at the bidirectional LMP-1/LMP-2B promoter. These results indicate that EBNA-3C directly activates the expression of LMP-1 and LMP-2B but is unlikely to significantly regulate EBNA expression via Cp under normal growth conditions. |
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| Grant Information: | P30 CA021765 United States CA NCI NIH HHS; R01 CA056645 United States CA NCI NIH HHS; CA21765 United States CA NCI NIH HHS; CA56645 United States CA NCI NIH HHS |
| Substance Nomenclature: | 0 (Antigens, Viral); 0 (DNA, Viral); 0 (DNA-Binding Proteins); 0 (Epstein-Barr Virus Nuclear Antigens); 0 (Proto-Oncogene Proteins); 0 (RNA, Viral); 0 (Trans-Activators); 0 (Transcription Factors); 0 (Viral Matrix Proteins); 0 (Viral Proteins); 0 (Proto-Oncogene Protein Spi-1); 0 (EBNA-2 protein, Human herpesvirus 4); 0 (EBNA-3C, epstein-barr virus); 0 (EBV-associated membrane antigen, Epstein-Barr virus); 148350-00-9 (SPIB protein, human) |
| Entry Date(s): | Date Created: 20060908 Date Completed: 20061204 Latest Revision: 20260128 |
| Update Code: | 20260130 |
| PubMed Central ID: | PMC1642179 |
| DOI: | 10.1128/JVI.00897-06 |
| PMID: | 16956945 |
| Database: | MEDLINE |
Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't