Regulation of viral and cellular gene expression by E1A proteins encoded by the oncogenic adenovirus type 12.

Abstract

For more than 15 years human adenoviruses (Ad) have been a powerful tool for studying cellular processes such as regulation of gene expression, alternative splicing, polyadenylation, and replication. Especially the analysis of viral proteins encoded by early region 1A (E1A), which was shown to regulate transcription, has given many insights into how DNA viruses regulate their own and cellular gene expression. Moreover, E1A proteins have been the subject of extensive studies because of their ability to act as oncoproteins that cooperate with the adenovirus E1B gene products to transform rodent cells in culture and, in case of the oncogenic adenoviruses (e.g., Ad12), to induce tumors in animals (Gallimore et al. 1974; Graham et al. 1974a, b; Houweling 1980; Jochemsen et al. 1982). The ability to promote oncogenic transformation and transcriptional regulation appear to be distinct activities of the E1A polypeptides (for review see Moran and Mathews 1987). In oncogenic transformation, protein functions of region E1A are necessary to immortalize primary cells, whereas functions of region E1B are essential to obtain a fully transformed phenotype. The functions of region E1B can be substituted by specific cellular gene products, e.g., activated Ha-ras (Byrd et al. 1988; Ruley 1983). The reasons for the difference in oncogenicity of variant adenovirus serotypes are not yet understood.KeywordsAdenovirus TypeCellular Gene ExpressionCellular Transcription FactorHuman Adenovirus TypeRetinoblastoma Gene ProductThese keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.