Transforming region of 243R E1A contains two overlapping but distinct transactivation domains

Nianli Sang, Pier Paolo Claudio, Yan Fu, Nobuo Horikoshi, Ullrich Graeven, Roberto Weinmann, Antonio Giordano

Research output: Contribution to journalArticle

5 Scopus citations

Abstract

Conserved regions 1 and 2 as well as the amino terminus of E1A are required for the transforming activity of the E1A oncoprotein. We show here that the amino terminus of 243R E1A has transactivation activity when brought to a promoter in yeast. Recruitment to a specific promoter is essential. Mutagenesis studies correlated the transactivation function with the extreme amino terminus and the conserved region 1 of E1A. Cotransfection assays in rodent cells confirmed that two overlapping but distinguishable domains, amino acids 1-65 and 37-80, can transactivate independently when targeted to a promoter. We also observed that when recruited to the proliferating cell nuclear antigen (PCNA) promoter, the amino-terminal region was sufficient to transactivate the PCNA promoter. On the other hand, deletion of the amino terminus of E1A resulted in failure to induce PCNA expression. Fusion of VP16 with the amino-terminal-deleted EIA mutant was able to restore the ability to induce the PCNA promoter. We further show that the amino-terminal region also is required for 243R E1A to repress the transactivation mediated by a universal transactivator DBD.VP16 and DBD.E1A. This repression could be specifically relieved by overexpression of TBP but not TFIIB. In addition, we show that the amino terminus of E1A is involved in in vitro interaction with the TATA binding protein (TBP). Thus the amino-terminal transforming region of EIA may regulate cellular gene expression in species that are distant in evolution via a common mechanism, functionally targeting TBP.

Original languageEnglish (US)
Pages (from-to)1321-1333
Number of pages13
JournalDNA and Cell Biology
Volume16
Issue number11
DOIs
StatePublished - 1997

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cell Biology

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