In Vitro Transcription: Probing the Molecular Functions of Adenovirus Regulatory Proteins

Adenoviruses (Ads), like other DNA tumor viruses, have evolved specific regulatory genes that facilitate virus replication by controlling the transcription of other viral genes as well as that of key cellular genes that regulate cell-cycle progression and cellular DNA synthesis. Of particular interest is the Ad E1A transcription unit that encodes two major proteins of 243 and 289 amino acids. The 289R protein is identical to the 243R protein except that it also contains conserved region 3 (CR3, residues 140–188), a powerful transcriptional activator of Ad early genes (see ref. 1 for review). The 243R protein encodes diverse biological functions, including the ability to induce cell-cycle progression, immortalize cells, transform cells in cooperation with other oncogenes, and paradoxically to inhibit tumorigenicity and cell differentiation (1 ). These E1A 243 R functions are encoded within multiple protein domains that can transcriptionally activate or repress cellular genes involved in the regulation of cell proliferation and cell differentiation.