The mechanism of complex formation between Fli-1 and SRF transcription factors

AUTOR(ES)

Dalgleish, Pamela

FONTE

Oxford University Press

RESUMO

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.

Documentos Relacionados

• Functional Cross-Antagonism between Transcription Factors FLI-1 and EKLF
• Negative and Translation Termination-Dependent Positive Control of FLI-1 Protein Synthesis by Conserved Overlapping 5′ Upstream Open Reading Frames in Fli-1 mRNA
• A protein domain conserved between yeast MCM1 and human SRF directs ternary complex formation.
• Direct regulation of BCL-2 by FLI-1 is involved in the survival of FLI-1-transformed erythroblasts
• Protein-Protein Interaction between Fli-1 and GATA-1 Mediates Synergistic Expression of Megakaryocyte-Specific Genes through Cooperative DNA Binding