Modular organization of the E2F1 activation domain and its interaction with general transcription factors TBP and TFIIH.
The transcriptional activator E2F1 regulates the expression of genes at the G1/S boundary. We have characterized interactions of the E2F1 activation domain with two general transcription factors, the TATA-box binding protein (TBP) and TFIIH. Two distinct binding sites on E2F1 were identified for TBP (amino acids 386-417 and 415-437) each ... of which supported activation in mammalian cells when expressed as a fusion to a heterologous DNA-binding domain. Neither of these minimal activation domains independently bound TFIIH; rather, the TFIIH binding site of E2F1 overlaps both domains. Loss of TFIIH-binding by E2F1 resulted in a 60-65% reduction in transactivation, suggesting that the E2F1/TFIIH interaction is important, but not essential, for transactivation. The retinoblastoma protein (Rb) binds directly to E2F1 and represses E2F1-mediated transactivation. We have demonstrated that recombinant Rb can compete with TBP and the p62 subunit of TFIIH for binding to immobilized E2F1. A tumorigenic form of Rb deficient in repressing E2F1-mediated transactivation is likewise deficient in displacing TBP from E2F1. We propose that competition between Rb and both TBP and TFIIH for binding to E2F1 is a mechanism by which Rb inhibits transactivation by E2F1.
Mesh Terms:
Binding Sites, Binding, Competitive, Carrier Proteins, Cell Cycle Proteins, Chromatography, Affinity, DNA-Binding Proteins, Drosophila Proteins, E2F Transcription Factors, E2F1 Transcription Factor, Fungal Proteins, Humans, Recombinant Fusion Proteins, Retinoblastoma Protein, Retinoblastoma-Binding Protein 1, Saccharomyces cerevisiae Proteins, TATA-Binding Protein Associated Factors, TATA-Box Binding Protein, Trans-Activators, Transcription Factor DP1, Transcription Factor TFIID, Transcription Factor TFIIH, Transcription Factors, Transcription Factors, TFII
Binding Sites, Binding, Competitive, Carrier Proteins, Cell Cycle Proteins, Chromatography, Affinity, DNA-Binding Proteins, Drosophila Proteins, E2F Transcription Factors, E2F1 Transcription Factor, Fungal Proteins, Humans, Recombinant Fusion Proteins, Retinoblastoma Protein, Retinoblastoma-Binding Protein 1, Saccharomyces cerevisiae Proteins, TATA-Binding Protein Associated Factors, TATA-Box Binding Protein, Trans-Activators, Transcription Factor DP1, Transcription Factor TFIID, Transcription Factor TFIIH, Transcription Factors, Transcription Factors, TFII
Oncogene
Date: Nov. 27, 1997
PubMed ID: 9400991
View in: Pubmed Google Scholar
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