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Updated: Aug 8, 2026

Mapping the Structure-Function Relationships of Disordered Oncogenic Transcription Factors Using Transcriptomic Analysis
Published on: June 27, 2020
Mutational and functional analysis of an essential subdomain of the adenovirus E1A N-terminal transcription
Paul M Loewenstein1, Sophia Arackal, Maurice Green
1Institute for Molecular Virology, Saint Louis University School of Medicine, St. Louis, MI 63110, USA.
Abstract:
Adenovirus early gene 1A (E1A) possesses a potent transcriptional repression function within the first 80 amino acids (E1A 1-80). Our previous analysis of subdomain 1 (residues 1 to 30) revealed strong correlations between residues required for repression and for disruption of TBP-TATA complexes. Here, we report a functional analysis of subdomain 2 (48 to 60) by alanine-scanning mutagenesis. 53Ala, 54Pro, 55Glu, and 56Asp are required for repression in vitro and in vivo and for efficient interaction with p300 but not for disruption of TBP-TATA. These combined results suggest a model for E1A transcription repression. E1A through subdomains 1 and 2 uses coactivators like p300 as scaffolds to access E1A repressible promoters. At the promoter, subdomain 1 interacts with TBP to disrupt TBP-TATA and abort transcription initiation. In further support of this model, we show that E1A 1-80 bound to the p300-binding site retains the ability to interact with TBP.
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