The Zinc Finger Region of the Adenovirus E1A Transactivating Domain Complexes with the TATA Box Binding Protein

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 91; no. 7; pp. 2488 - 2492
• Main Authors: Geisberg, Jospeph V., Lee, Wes S., Berk, Arnold J., Ricciardi, Robert P.
• Format: Journal Article Conference Proceeding
• Language: English
• Published: Washington, DC National Academy of Sciences of the United States of America 29-03-1994; National Acad Sciences; National Academy of Sciences
• Subjects: adenovirus; Adenovirus E1A Proteins - metabolism; Adenoviruses; Amino Acid Sequence; Biochemistry; Biological and medical sciences; DNA Mutational Analysis; DNA-Binding Proteins - metabolism; Fundamental and applied biological sciences. Psychology; Genetic mutation; Genetics; Medical research; Microbiology; Models, Genetic; Molecular Sequence Data; Phenotypes; Promoter regions; Protein Binding; Proteins; RNA; TATA Box; TATA-Box Binding Protein; Transactivation; Transcription factors; Transcription Factors - metabolism; Transcriptional Activation; Virology; Viruses; Zinc; Zinc Fingers; Virus; Binding protein; Adenoviridae; Transcription; Structure activity relation; Zinc finger structure; Molecular interaction; Activation; Gene expression; Transcription factor
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.91.7.2488

The 289R E1A protein of adenovirus trans-activates 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.