ABSTRACT
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.
Subject(s)
DNA-Binding Proteins/metabolism , Nuclear Proteins/metabolism , Proto-Oncogene Proteins , Trans-Activators/metabolism , 3T3 Cells , Amino Acid Sequence , Animals , Binding Sites , DNA-Binding Proteins/genetics , Humans , Mice , Molecular Sequence Data , Mutagenesis, Site-Directed , Nuclear Proteins/genetics , Protein Binding , Proto-Oncogene Protein c-fli-1 , Sequence Homology, Amino Acid , Serum Response FactorABSTRACT
General practitioners in the Northampton area were asked to assess the various meetings of a programme of continuing education they had attended between May 1969 and May 1970. Analysis of their replies suggests that meetings which depend on previous study and encourage participation are most likely to be successful.
