TRANSCRIPTION FACTOR TFIID IS A DIRECT FUNCTIONAL TARGET OF THE ADENOVIRUS E1A TRANSCRIPTION-REPRESSION DOMAIN

The 243-amino acid adenovirus E1A oncoprotein both positively and nega tively modulates the expression of cellular genes involved in the regu lation of cell growth. The E1A transcription repression function appea rs to be linked with its ability to induce cellular DNA synthesis, cel l proliferation, and cell transformation, as well as to inhibit cell d ifferentiation. The mechanism by which E1A represses the transcription of various promoters has proven enigmatic. Here we provide several li nes of evidence that the ''TATA-box'' binding protein (TBP) component of transcription factor TFIID is a cellular target of the E1A repressi on function encoded within the E1A N-terminal 80 amino acids. (i) The E1A N-terminal 80 amino acids [E1A-(1-80)protein] efficiently represse s basal transcription from TATA-containing core promoters in vitro. (i i) TBP reverses completely E1A repression in vitro. (iii) TBP restores transcriptional activity to E1A-(1-80) protein affinity-depleted nucl ear extracts. (iv) The N-terminal repression domain of E1A interacts d irectly and specifically with TBP in vitro. These results may help exp lain how E1A represses a set of genes that lack common upstream promot er elements.