27 Adenovirus E1A trans-Activation: Understanding It Will Require Learning How the General Transcription Factors Function

Abstract

OVERVIEW
Adenovirus E1A protein stimulates transcription from a variety of promoters composed of binding sites for several different cellular transcription factors (TFs). This could be accomplished if E1A increased the activity of a general transcription factor. TFIID binds to TATA boxes and initiates the ordered assembly of other general transcription factors and RNA polymerase II. TFIID is also required for transcription from some TATA-less promoters. TFIID activity is increased in extracts of adenovirus-infected cells and may be the general factor targeted by E1A. Recent results show that E1A binds specifically to TFIID. Consequently, E1A may activate transcription from multiple promoters by binding to TFIID and modifying its function. E1A may also perform other functions that increase the activity of promoter-specific factors.

INTRODUCTION
The adenovirus 2 large E1A protein is a powerful activator of viral transcription (Jones and Shenk 1979). Unlike most transcription factors that have been studied in detail, it stimulates transcription from a very broad set of promoters. The E1A region maps near the left end of the 36-kb linear double-stranded DNA viral genome. During the early phase of infection, the RNA transcribed from this region is spliced into two predominant alternative mRNAs of 13S and 12S (Perricaudet et al. 1979). The 13S mRNA encodes an acidic nuclear phosphorylated protein of 289 residues. The 12S mRNA encodes a related nuclear phosphoprotein of 243 residues, identical in sequence to the larger protein except for 46 residues deleted from near the middle of the protein as a consequence of the altered...