Essential Role of Rbp-jkappa in Activation of the K8 Delayed-early Promoter of Kaposi's Sarcoma-associated Herpesvirus by Orf50/Rta.
From: Department of Microbiology, School of Dental Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Virology
- Publish Date: Mar 2007
- ISSN: 0042-6822
- Volume: 359
- Issue: 1
- Pages: 19-27
- Medium: Print
- Language: English
- Citation (JAMA): Wang Yan, Yuan Yan, et al. Essential Role of Rbp-jkappa in Activation of the K8 Delayed-early Promoter of Kaposi's Sarcoma-associated Herpesvirus by Orf50/Rta.. Virology Mar 2007;359:19-27
Abstract
KSHV K8 gene is activated by virally encoded transactivator RTA in delayed-early stage of viral reactivation. Three RTA-responsive elements (RREs) were identified in the promoter. Among them, RRE-II was found to be the most critical cis-acting element for RTA transactivation. In this report, the mechanism underlying RTA-mediated activation of the K8 delayed-early promoter was investigated. A DNA affinity purification study demonstrated that RRE-II was bound by cellular protein RBP-Jkappa, a sequence-specific DNA binding protein and a primary target of the Notch signaling pathway. Inspection of the RRE-II sequence revealed a potential recognition sequence for RBP-Jkappa (GTGAGAA) between the nucleotides -102 and -108 relative to the transcription initial site. Removal or mutation of the motif abolished RBP-Jkappa binding to the K8 promoter and as a consequence, RTA failed to bind to and activate the promoter. An essential role of RBP-Jkappa in the transcription of the K8 promoter was demonstrated by diminishment of the promoter activity in RBP-Jkappa-null murine embryonic fibroblasts. Taken together, RTA activates the K8 promoter through an indirect binding mechanism, i.e. being recruited to the K8 promoter through interaction with RBP-Jkappa bound to an RBP-Jkappa motif in the promoter.
Mesh Headings (Keywords): Animals, Basic-Leucine Zipper Transcription Factors, Binding Sites, Cell Line, DNA-Binding Proteins, Gene Expression Regulation, Viral, Herpesvirus 8, Human, Humans, Immediate-Early Proteins, Immunoglobulin J Recombination Signal Sequence-Binding Protein, Mice, Open Reading Frames, Point Mutation, Promoter Regions (Genetics), Repressor Proteins, Sequence Deletion, Trans-Activators, Viral Proteins, Virus Activation
Check for Full Text / PubMed Unique Identifier (PMID): 17055026
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