PubMed:10022850 JSONTXT

{"project":"PMID_GLOBAL","denotations":[{"id":"T1","span":{"begin":208,"end":211},"obj":"DiseaseOrPhenotypicFeature"},{"id":"T2","span":{"begin":356,"end":359},"obj":"DiseaseOrPhenotypicFeature"},{"id":"T3","span":{"begin":453,"end":456},"obj":"DiseaseOrPhenotypicFeature"},{"id":"T4","span":{"begin":509,"end":512},"obj":"DiseaseOrPhenotypicFeature"},{"id":"T5","span":{"begin":829,"end":832},"obj":"DiseaseOrPhenotypicFeature"},{"id":"T6","span":{"begin":892,"end":896},"obj":"DiseaseOrPhenotypicFeature"},{"id":"T7","span":{"begin":908,"end":911},"obj":"DiseaseOrPhenotypicFeature"},{"id":"T8","span":{"begin":1369,"end":1372},"obj":"DiseaseOrPhenotypicFeature"},{"id":"T9","span":{"begin":1373,"end":1376},"obj":"DiseaseOrPhenotypicFeature"},{"id":"T10","span":{"begin":1485,"end":1488},"obj":"DiseaseOrPhenotypicFeature"},{"id":"T11","span":{"begin":1544,"end":1547},"obj":"DiseaseOrPhenotypicFeature"}],"attributes":[{"id":"A1","pred":"mondo_id","subj":"T1","obj":"0012833"},{"id":"A2","pred":"mondo_id","subj":"T2","obj":"0012833"},{"id":"A3","pred":"mondo_id","subj":"T3","obj":"0010565"},{"id":"A4","pred":"mondo_id","subj":"T4","obj":"0010565"},{"id":"A5","pred":"mondo_id","subj":"T5","obj":"0010565"},{"id":"A6","pred":"mondo_id","subj":"T6","obj":"0015404"},{"id":"A7","pred":"mondo_id","subj":"T7","obj":"0010565"},{"id":"A8","pred":"mondo_id","subj":"T8","obj":"0010565"},{"id":"A9","pred":"mondo_id","subj":"T9","obj":"0012833"},{"id":"A10","pred":"mondo_id","subj":"T10","obj":"0010565"},{"id":"A11","pred":"mondo_id","subj":"T11","obj":"0010565"}],"text":"The amino-terminal C/H1 domain of CREB binding protein mediates zta transcriptional activation of latent Epstein-Barr virus.\nLatent Epstein-Barr virus (EBV) is maintained as a nucleosome-covered episome that can be transcriptionally activated by overexpression of the viral immediate-early protein, Zta. We show here that reactivation of latent EBV by Zta can be significantly enhanced by coexpression of the cellular coactivators CREB binding protein (CBP) and p300. A stable complex containing both Zta and CBP could be isolated from lytically stimulated, but not latently infected RAJI nuclear extracts. Zta-mediated viral reactivation and transcriptional activation were both significantly inhibited by coexpression of the E1A 12S protein but not by an N-terminal deletion mutation of E1A (E1ADelta2-36), which fails to bind CBP. Zta bound directly to two related cysteine- and histidine-rich domains of CBP, referred to as C/H1 and C/H3. These domains both interacted specifically with the transcriptional activation domain of Zta in an electrophoretic mobility shift assay. Interestingly, we found that the C/H3 domain was a potent dominant negative inhibitor of Zta transcriptional activation function. In contrast, an amino-terminal fragment containing the C/H1 domain was sufficient for coactivation of Zta transcription and viral reactivation function. Thus, CBP can stimulate the transcription of latent EBV in a histone acetyltransferase-independent manner mediated by the CBP amino-terminal C/H1-containing domain. We propose that CBP may regulate aspects of EBV latency and reactivation by integrating cellular signals mediated by competitive interactions between C/H1, C/H3, and the Zta activation domain."}

{"project":"FSU-PRGE","denotations":[{"id":"T1","span":{"begin":34,"end":54},"obj":"protein"},{"id":"T2","span":{"begin":64,"end":67},"obj":"protein"},{"id":"T3","span":{"begin":299,"end":302},"obj":"protein"},{"id":"T4","span":{"begin":352,"end":355},"obj":"protein"},{"id":"T5","span":{"begin":431,"end":451},"obj":"protein"},{"id":"T6","span":{"begin":453,"end":456},"obj":"protein"},{"id":"T7","span":{"begin":462,"end":466},"obj":"protein"},{"id":"T8","span":{"begin":501,"end":504},"obj":"protein"},{"id":"T9","span":{"begin":509,"end":512},"obj":"protein"},{"id":"T10","span":{"begin":607,"end":610},"obj":"protein"},{"id":"T11","span":{"begin":727,"end":734},"obj":"protein"},{"id":"T12","span":{"begin":789,"end":792},"obj":"protein"},{"id":"T13","span":{"begin":829,"end":832},"obj":"protein"},{"id":"T14","span":{"begin":834,"end":837},"obj":"protein"},{"id":"T15","span":{"begin":908,"end":911},"obj":"protein"},{"id":"T16","span":{"begin":1032,"end":1035},"obj":"protein"},{"id":"T17","span":{"begin":1169,"end":1172},"obj":"protein"},{"id":"T18","span":{"begin":1312,"end":1315},"obj":"protein"},{"id":"T19","span":{"begin":1369,"end":1372},"obj":"protein"},{"id":"T20","span":{"begin":1424,"end":1449},"obj":"protein"},{"id":"T21","span":{"begin":1485,"end":1488},"obj":"protein"},{"id":"T22","span":{"begin":1544,"end":1547},"obj":"protein"},{"id":"T23","span":{"begin":1698,"end":1701},"obj":"protein"}],"text":"The amino-terminal C/H1 domain of CREB binding protein mediates zta transcriptional activation of latent Epstein-Barr virus.\nLatent Epstein-Barr virus (EBV) is maintained as a nucleosome-covered episome that can be transcriptionally activated by overexpression of the viral immediate-early protein, Zta. We show here that reactivation of latent EBV by Zta can be significantly enhanced by coexpression of the cellular coactivators CREB binding protein (CBP) and p300. A stable complex containing both Zta and CBP could be isolated from lytically stimulated, but not latently infected RAJI nuclear extracts. Zta-mediated viral reactivation and transcriptional activation were both significantly inhibited by coexpression of the E1A 12S protein but not by an N-terminal deletion mutation of E1A (E1ADelta2-36), which fails to bind CBP. Zta bound directly to two related cysteine- and histidine-rich domains of CBP, referred to as C/H1 and C/H3. These domains both interacted specifically with the transcriptional activation domain of Zta in an electrophoretic mobility shift assay. Interestingly, we found that the C/H3 domain was a potent dominant negative inhibitor of Zta transcriptional activation function. In contrast, an amino-terminal fragment containing the C/H1 domain was sufficient for coactivation of Zta transcription and viral reactivation function. Thus, CBP can stimulate the transcription of latent EBV in a histone acetyltransferase-independent manner mediated by the CBP amino-terminal C/H1-containing domain. We propose that CBP may regulate aspects of EBV latency and reactivation by integrating cellular signals mediated by competitive interactions between C/H1, C/H3, and the Zta activation domain."}