Epstein-Barr Virus Polymerase Processivity Factor Enhances BALF2 Promoter Transcription as a Coactivator for the BZLF1 Immediate-Early Protein
Open Access
- 7 August 2009
- journal article
- Published by Elsevier BV
- Vol. 284 (32), 21557-21568
- https://doi.org/10.1074/jbc.m109.015685
Abstract
The Epstein-Barr virus (EBV) BMRF1 protein is an essential replication protein acting at viral replication forks as a viral DNA polymerase processivity factor, whereas the BALF2 protein is a single-stranded DNA-binding protein that also acts at replication forks and is most abundantly expressed during viral productive replication. Here we document that the BMRF1 protein evidently enhances viral BZLF1 transcription factor-mediated transactivation of the BALF2 gene promoter. Mutagenesis and electrophoretic mobility shift assays demonstrated the BALF2 promoter to harbor two BZLF1 protein-binding sites (BZLF1-responsive elements). Direct binding of the BZLF1 protein to BZLF1-responsive elements and physical interaction between BZLF1 and BMRF1 proteins are prerequisite for the BMRF1 protein up-regulation of the BALF2 gene promoter. A monomeric mutant, C95E, which is defective in homodimerization, could still interact and enhance BZLF1-mediated transactivation. Furthermore although EBV protein kinase phosphorylates BMRF1 protein extensively, it turned out that phosphorylation of the protein by the kinase is inhibitory to the enhancement of the BZLF1-mediated transactivation of BALF2 promoter. Exogenous expression of BMRF1 protein augmented BALF2 expression in HEK293 cells harboring the EBV genome but lacking BMRF1 and BALF5 genes, demonstrating functions as a transcriptional regulator in the context of viral infection. Overall the BMRF1 protein is a multifunctional protein that cannot only act as a DNA polymerase processivity factor but also enhances BALF2 promoter transcription as a coactivator for the BZLF1 protein, regulating the expression level of viral single-stranded DNA-binding protein.Keywords
This publication has 36 references indexed in Scilit:
- Effect of phosphorylation on the transactivation activity of Epstein–Barr virus BMRF1, a major target of the viral BGLF4 kinaseJournal of General Virology, 2008
- Noncanonical TATA Sequence in the UL44 Late Promoter of Human Cytomegalovirus Is Required for the Accumulation of Late Viral TranscriptsJournal of Virology, 2008
- Epstein-Barr Virus-Encoded Protein Kinase (BGLF4) Is Involved in Production of Infectious VirusJournal of Virology, 2007
- Structural Basis of Lytic Cycle Activation by the Epstein-Barr Virus ZEBRA ProteinMolecular Cell, 2006
- Detection of Epstein–Barr virus BGLF4 protein kinase in virus replication compartments and virus particlesJournal of General Virology, 2005
- Architecture of Replication Compartments Formed during Epstein-Barr Virus Lytic ReplicationJournal of Virology, 2005
- The Epstein-Barr Virus Protein BMRF1 Activates Gastrin TranscriptionJournal of Virology, 2005
- The Cytomegalovirus DNA Polymerase Subunit UL44 Forms a C Clamp-Shaped DimerMolecular Cell, 2004
- Identification of protein kinases responsible for phosphorylation of Epstein–Barr virus nuclear antigen leader protein at serine-35, which regulates its coactivator functionJournal of General Virology, 2003
- Identification and characterization of oriLyt, a lytic origin of DNA replication of Epstein-Barr virusCell, 1988