title: The zinc finger region of the adenovirus E1A transactivating domain complexes with the TATA box binding protein.
abstract: The 289R E1A protein of adenovirus transactivates a variety of viral and cellular promoters through protein-protein interactions. In earlier studies, mutational analyses of the E1A transactivating domain identified residues that are critical for transactivation and implied that the zinc finger region of the transactivating domain binds a transcription factor. Also, the E1A activation domain was found to bind to the TATA box binding protein (TBP) in vitro. Here, we tested the significance of the E1A-TBP interaction for E1A transactivation by analyzing the effects of conservative substitutions at each of the 49 residues of the E1A activation domain. Seven of the substitutions significantly diminished TBP binding in vitro. All of these were in the zinc finger region and were defective for transactivation in vivo. The perfect correlation between reduced TBP binding and transactivation argues strongly that a direct interaction between the E1A activation domain and TBP is critical to the mechanism of E1A activation. This genetic analysis leads us to further suggest that another factor, which is limiting, is also necessary for E1A-mediated transactivation.
authors.affiliation: Department of Microbiology, School of Dental Medicine, University of Pennsylvania, Philadelphia 19104.
authors.forename: J V
authors.initials: JV
authors.lastname: Geisberg
authors.forename: W S
authors.initials: WS
authors.lastname: Lee
authors.forename: A J
authors.initials: AJ
authors.lastname: Berk
authors.forename: R P
authors.initials: RP
authors.lastname: Ricciardi
mesh_terms: D017500:Adenovirus E1A Proteins / Q000378:metabolism*; D000595:Amino Acid Sequence; D004252:DNA Mutational Analysis; D004268:DNA-Binding Proteins / Q000378:metabolism*; D008957:Models, Genetic; D008969:Molecular Sequence Data; D011485:Protein Binding; D016385:TATA Box; D035181:TATA-Box Binding Protein; D014157:Transcription Factors / Q000378:metabolism*; D015533:Transcriptional Activation; D016335:Zinc Fingers
chemical_list: D017500:Adenovirus E1A Proteins; D004268:DNA-Binding Proteins; D035181:TATA-Box Binding Protein; D014157:Transcription Factors