RESUMO
The Epstein-Barr virus (EBV) genome codes for several transcriptional trans-activators. One of them, the BZLF1 open reading frame (ORF)-encoded product EB1, is able to induce the productive cycle in infected B cells. From the cloning and characterization of full-length cDNAs, we found that EB1 could be made from three overlapping messenger RNAs expressed under the control of two different promoters that we call P1 and P2. The first mRNA, 1 kb long, is made from the P1 promoter and codes for EB1 alone. The two other mRNAs, respectively 3 and 4 kb long and made by facultative splicing, are bicistronic mRNAs. They code not only for the trans-activator EB1 but also for a second EBV transcriptional trans-activator R, encoded by the BRLF1 ORF. In effect, authentic EB1 and R proteins are expressed from the 3 and 4 kb long cDNAs as demonstrated by identification of the proteins with specific antisera. In addition, EB1 and R expressed from the 3 and 4 kb cDNAs activate transcription from their specific targets in the EBV early promoter DR.
Assuntos
Herpesvirus Humano 4/genética , RNA Mensageiro/genética , Fatores de Transcrição/genética , Linhagem Celular Transformada , Mapeamento Cromossômico , DNA/genética , Elementos Facilitadores Genéticos , Regulação da Expressão Gênica , Produtos do Gene tat , Genes Virais , Humanos , Plasmídeos , Splicing de RNA , RNA Viral/genética , TransfecçãoRESUMO
When expressed in Epstein-Barr virus (EBV) latently infected B cells, the EBV early protein EB1 trans-activates as many EBV early genes as does TPA. Several EB1 responsive elements (ZRE) have been identified in EBV early promoters and are located at relatively short distances from the TATA box. One of them (ZRE-M) overlaps with a consensus TPA responsive element (TRE) defined as an AP-1/c-jun/c-fos binding site and is located in an EBV promoter controlling the expression of the post-transcriptional activator EB2. Another (ZREZ) is located in the promoter controlling the expression of EB1 and does not respond to TPA. These two ZREs have no apparent sequence homology. Although EB1 activates transcription from the AP-1 enhancer sequence and from the ZREZ, the activation is severely impaired by distance, suggesting that EB1 is more likely to be a promoter factor than an enhancer factor. These properties also suggest that EB1 is not functionally related to c-jun and c-fos. However, since EB1 can activate transcription from AP-1 binding sites when properly positioned, the role of this factor in the oncogenic properties of EBV should be considered.
Assuntos
Proteínas de Ligação a DNA/genética , Herpesvirus Humano 4/genética , Fatores de Transcrição/genética , Transcrição Gênica , Sequência de Bases , Sítios de Ligação , DNA Viral/genética , Proteínas de Ligação a DNA/metabolismo , Regulação da Expressão Gênica/efeitos dos fármacos , Produtos do Gene tat , Genes Virais , Herpesvirus Humano 4/metabolismo , Dados de Sequência Molecular , Mutação , Regiões Promotoras Genéticas/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-jun , Acetato de Tetradecanoilforbol/farmacologia , Fatores de Transcrição/metabolismoRESUMO
A simultaneous decay of the expression of Im 140 kDa, Im 150 kDa and Im 160 kDa high MW membrane antigens, concomitant with the cell proliferation arrest, was observed during erythropoietin induced differentiation of ts 34 AEV-transformed erythroid cells cultivated at the restrictive temperature. Expression of embryo-immature antigens was maintained during induced differentiation of erythroleukemia cells, but their MW shifted from 50 to 48 kDa, which corresponds to the MW of embryo-immature antigens detected on normal erythroid cells. In the absence of erythropoietin at the restrictive temperature, conditions under which the ts 34 AEV-transformed erythroid cells fail to differentiate and maintain their capacity to proliferate, the expression of high MW antigens as well as the expression of embryo-immature antigens remained unaffected. Therefore, it is shown that the expression of specific membrane antigens is modulated under conditions rendering the erythroleukemia cell differentiation process possible.
