The mechanism of complex formation between Fli-1 and SRF transcription factors.
The mechanisms of multicomponent transcription factor complex assembly are currently poorly defined. A paradigm for this type of complex is the ETS-domain transcription factor Elk-1 and the MADS-box transcription factor SRF which form a ternary complex with the c- fos serum response element (SRE). In this study we have analysed how a different ETS-domain transcription factor Fli-1 interacts with SRF to form ternary complexes with this element. Two regions of Fli-1 that are required for ternary complex formation have been identified. These SRF binding motifs are located on either side of the ETS DNA-binding domain. Hydrophobic amino acids within these motifs have been identified that play important roles in binding to SRF and ternary complex formation. By using Fli-1 derivatives with mutations in the N-terminal SRF binding motif, the significance of Fli-1-SRF interactions in recruitment of Fli-1 to the c- fos SRE in vivo has been demonstrated. Collectively our data provide a model of how Fli-1 interacts with SRF that differs significantly from the mechanism used by a different ETS-domain protein, Elk-1.
Dalgleish
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Department of Biochemistry, The Medical School, University of Newcastle upon Tyne, Newcastle upon Tyne NE2 4HH, UK.
Sharrocks
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D016475:3T3 Cells; D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D051789:Proto-Oncogene Protein c-fli-1; D011518:Proto-Oncogene Proteins; D017386:Sequence Homology, Amino Acid; D026362:Serum Response Factor; D015534:Trans-Activators / Q000378:metabolism*
D004268:DNA-Binding Proteins; C497426:Fli1 protein, mouse; D009687:Nuclear Proteins; D051789:Proto-Oncogene Protein c-fli-1; D011518:Proto-Oncogene Proteins; D026362:Serum Response Factor; D015534:Trans-Activators