Mutational and functional analysis of an essential subdomain of the adenovirus E1A N-terminal transcription repression domain
| Autor: | Sophia Arackal, Maurice Green, Paul M. Loewenstein |
|---|---|
| Rok vydání: | 2006 |
| Předmět: |
Transcription repression
Transcription Genetic viruses p300 macromolecular substances Biology environment and public health Cell Line Tumor Virology Humans Adenovirus TBP Psychological repression Gene Genetics chemistry.chemical_classification Functional analysis Mutagenesis Promoter Mutational analysis In vitro Protein Structure Tertiary Cell biology Amino acid Repressor Proteins Ad E1A Gene Expression Regulation chemistry Mutation Adenovirus E1A Proteins Function (biology) |
| Zdroj: | Virology. 351:312-321 |
| ISSN: | 0042-6822 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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