The Epstein-Barr virus BZLF1 protein interacts physically and functionally with the histone acetylase CREB-binding protein.
The Epstein-Barr virus (EBV) immediate-early protein BZLF1 (Z) is a key regulator of the EBV latent-to-lytic switch. Z is a transcriptional activator which induces EBV early gene expression. We demonstrate here that Z interacts with CREB-binding protein (CBP), a histone acetylase and transcriptional coactivator. This interaction requires the amino-terminal region of CBP as well as the transactivation and leucine zipper domains of Z. We show that CBP enhances Z-mediated transactivation of EBV early promoters, in reporter gene assays and in the context of the endogenous genome. We also demonstrate that Z decreases CREB transactivation function and that this inhibitory effect is reversed by overexpression of CBP. We show that Z also interacts directly with CREB. However, mutational analysis indicates that Z inhibition of CREB activity requires the direct interaction between Z and CBP but not the direct interaction between Z and CREB. We propose that Z interacts with CBP to enhance viral early gene transcription. In addition, the Z-CBP interaction may control host cellular transcription factor activity through competition for limiting amounts of cellular CBP.
Adamson
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Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599-7295, USA.
Kenney
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D000123:Acetyltransferases / Q000378:metabolism*; D000818:Animals; D000956:Antigens, Viral / Q000235:genetics; D001665:Binding Sites; D050882:CREB-Binding Protein; D004268:DNA-Binding Proteins / Q000378:metabolism*; D015967:Gene Expression Regulation, Viral; D005814:Genes, Viral; D006367:HeLa Cells; D004854:Herpesvirus 4, Human / Q000235:genetics / Q000378:metabolism*; D051548:Histone Acetyltransferases; D006801:Humans; D009687:Nuclear Proteins / Q000378:metabolism*; D011817:Rabbits; D029701:Saccharomyces cerevisiae Proteins; D015534:Trans-Activators / Q000378:metabolism*; D014407:Tumor Cells, Cultured; D014764:Viral Proteins / Q000235:genetics; D017735:Virus Latency
D000956:Antigens, Viral; C083278:BHRF1 protein, Human herpesvirus 4; C063676:BZLF1 protein, Herpesvirus 4, Human; D004268:DNA-Binding Proteins; C083204:Epstein-Barr virus early antigen diffuse component; D009687:Nuclear Proteins; D029701:Saccharomyces cerevisiae Proteins; D015534:Trans-Activators; D014764:Viral Proteins; D000123:Acetyltransferases; D050882:CREB-Binding Protein; C494363:CREBBP protein, human; D051548:Histone Acetyltransferases