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.
Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599-7295, USA.
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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