c-Fos-induced activation of a TATA-box-containing promoter involves direct contact with TATA-box-binding protein.
Transcriptional activation in eukaryotes involves protein-protein interactions between regulatory transcription factors and components of the basal transcription machinery. Here we show that c-Fos, but not a related protein, Fra-1, can bind the TATA-box-binding protein (TBP) both in vitro and in vivo and that c-Fos can also interact with the transcription ... factor IID complex. High-affinity binding to TBP requires c-Fos activation modules which cooperate to activate transcription. One of these activation modules contains a TBP-binding motif (TBM) which was identified through its homology to TBP-binding viral activators. This motif is required for transcriptional activation, as well as TBP binding. Domain swap experiments indicate that a domain containing the TBM can confer TBP binding on Fra-1 both in vitro and in vivo. In vivo activation experiments indicate that a GAL4-Fos fusion can activate a promoter bearing a GAL4 site linked to a TATA box but that this activity does not occur at high concentrations of GAL4-Fos. This inhibition (squelching) of c-Fos activity is relieved by the presence of excess TBP, indicating that TBP is a direct functional target of c-Fos. Removing the TBM from c-Fos severely abrogates activation of a promoter containing a TATA box but does not affect activation of a promoter driven only by an initiator element. Collectively, these results suggest that c-Fos is able to activate via two distinct mechanisms, only one of which requires contact with TBP. Since TBP binding is not exhibited by Fra-1, TBP-mediated activation may be one characteristic that discriminates the function of Fos-related proteins.
Mesh Terms:
Adenovirus E1A Proteins, Amino Acid Sequence, Base Sequence, Binding Sites, DNA-Binding Proteins, Gene Expression Regulation, Herpes Simplex Virus Protein Vmw65, Macromolecular Substances, Molecular Sequence Data, Oligodeoxyribonucleotides, Promoter Regions, Genetic, Protein Binding, Proto-Oncogene Proteins c-fos, Sequence Alignment, Sequence Homology, Amino Acid, TATA-Box Binding Protein, Transcription Factor TFIID, Transcription Factors
Adenovirus E1A Proteins, Amino Acid Sequence, Base Sequence, Binding Sites, DNA-Binding Proteins, Gene Expression Regulation, Herpes Simplex Virus Protein Vmw65, Macromolecular Substances, Molecular Sequence Data, Oligodeoxyribonucleotides, Promoter Regions, Genetic, Protein Binding, Proto-Oncogene Proteins c-fos, Sequence Alignment, Sequence Homology, Amino Acid, TATA-Box Binding Protein, Transcription Factor TFIID, Transcription Factors
Mol. Cell. Biol.
Date: Sep. 01, 1994
PubMed ID: 8065335
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