Abstract:
Most viruses express proteins that ensure efficient expression of viral genes. The E1a protein of adenovirus is essential for the efficient transcription of early adenoviral genes. Three regions of E1a are conserved among different adenovirus E1a proteins. Region 3 alone is sufficient to induce transcription of early viral genes to a high level. This region is quite small (about 50 amino acids), but it functions like larger, cellular activators. It contains both an activating region and a binding region. The binding region of E1a determines its specificity and the activating region enables E1a to stimulate transcription. Both the activating and binding regions are highly ordered and require a common metal binding domain. Two other conserved regions of E1a (regions 1 and 2) stimulate transcription of viral and cellular genes to a low level. At least one promoter activated by regions 1 and 2 is not activated by region 3. We suggest that E1a contains two independent activators: region 3, on the one hand, and regions 1 and 2 on the other. The presence of two activators within one protein makes E1a a more promiscuous activator than most. Many DNA viruses express proteins that induce the infected cell to replicate its DNA, perhaps to generate the enzymes and metabolites essential to efficient viral replication. This is true for adenovirus, and the protein responsible is E1a. Regions 1 and 2 of E1a are essential for this activity. We have also examined transcriptional activators of two other viruses; the pseudorabies virus and human T cell leukemia virus type I. We find that these activators, like E1a region 3, contain an activating region that catalyzes transcription when positioned near a promoter. The activating region of pseudorabies virus immediate early protein is quite strong: as strong as that of VP16, a herpes simplex virion protein. (Full text available from University Microfilms International, Ann Arbor, MI, as Order No. AAD91-13187).
Keywords: *Genes, Viral HTLV-I/GENETICS Oncogene Proteins, Viral/*PHARMACOLOGY Pseudorabies/GENETICS Trans-Activators/*PHARMACOLOGY Transcription, Genetic/*DRUG EFFECTS THESIS
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