Epstein-Barr virus nuclear protein 2 interacts with p300, CBP, and PCAF histone acetyltransferases in activation of the LMP1 promoter.
The Epstein-Barr virus (EBV) nuclear protein 2 (EBNA2) and herpes simplex virion protein 16 (VP16) acidic domains that mediate transcriptional activation now are found to have affinity for p300, CBP, and PCAF histone acetyltransferases (HATs). Transcriptionally inactive point mutations in these domains lack affinity for p300, CBP, or PCAF. P300 and CBP copurify with the principal HAT activities that bind to EBNA2 or VP16 acidic domains through velocity sedimentation and anion-exchange chromatography. EBNA2 binds to both the N- and C-terminal domains of p300 and coimmune-precipitates from transfected 293T cells with p300. In EBV-infected Akata Burkitt's tumor cells that do not express the EBV encoded oncoproteins EBNA2 or LMP1, p300 expression enhances the ability of EBNA2 to up-regulate LMP1 expression. Through its intrinsic HAT activity, PCAF can further potentiate the p300 effect. In 293 T cells, P300 and CBP (but not PCAF) can also coactivate transcription mediated by the EBNA2 or VP16 acidic domains and HAT-negative mutants of p300 have partial activity. Thus, the EBNA2 and VP16 acidic domains can utilize the intrinsic HAT or scaffolding properties of p300 to activate transcription.
Wang
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Program in Virology, Department of Medicine Brigham and Women's Hospital, Harvard Medical School, Channing Laboratory, 181 Longwood Avenue, Boston, MA 02115, USA.
Grossman
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SR
Kieff
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D000123:Acetyltransferases / Q000378:metabolism*; D002051:Burkitt Lymphoma; D050882:CREB-Binding Protein; D018797:Cell Cycle Proteins / Q000378:metabolism*; D004268:DNA-Binding Proteins; D019309:Epstein-Barr Virus Nuclear Antigens; D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism; D015967:Gene Expression Regulation, Viral / Q000235:genetics; D017930:Genes, Reporter; D017405:Herpes Simplex Virus Protein Vmw65 / Q000378:metabolism; D004854:Herpesvirus 4, Human / Q000378:metabolism*; D051548:Histone Acetyltransferases; D006801:Humans; D009154:Mutation; D009687:Nuclear Proteins / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D029701:Saccharomyces cerevisiae Proteins; D015534:Trans-Activators / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D015533:Transcriptional Activation / Q000235:genetics; D014407:Tumor Cells, Cultured; D014763:Viral Matrix Proteins / Q000235:genetics*; D014764:Viral Proteins / Q000378:metabolism*; D050880:p300-CBP Transcription Factors; D000099224:p300-CBP-Associated Factor
D000123:Acetyltransferases; D050882:CREB-Binding Protein; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D019309:Epstein-Barr Virus Nuclear Antigens; D005656:Fungal Proteins; D017405:Herpes Simplex Virus Protein Vmw65; D051548:Histone Acetyltransferases; D009687:Nuclear Proteins; D029701:Saccharomyces cerevisiae Proteins; D015534:Trans-Activators; D014157:Transcription Factors; D014763:Viral Matrix Proteins; D014764:Viral Proteins; D050880:p300-CBP Transcription Factors; D000099224:p300-CBP-Associated Factor; C402641:EBNA-2 protein, Human herpesvirus 4; C037662:EBV-associated membrane antigen, Epstein-Barr virus; C052130:GAL4 protein, S cerevisiae; C494363:CREBBP protein, human