Related Experiment Videos
Muscle homeodomain protein MHox inhibits ternary complex formation at the c-fos serum response element
Abstract:
The Serum Response Element in the c-fos promoter is the target of growth factor-regulated signal transduction pathways. The ternary complex of Serum Response Element-binding protein Serum Response Factor and its accessory protein Ternary Complex Factor are important for transcriptional stimulation of the c-fos promoter in fibroblasts. However, this promoter is repressed in differentiating muscle cells. We discovered that MHox, a muscle homeodomain protein, was capable of inhibiting formation of the ternary complex by direct physical interaction between MHox and Serum Response Factor accessory protein-1 (SAP-1), one member of the Ternary Complex Factor family of proteins. Furthermore, exogenous MHox protein inhibited serum-inducibility of a Serum Response Element-dependent reporter gene in permeabilized fibroblasts. Taken together, these results imply that MHox is involved in blocking mitogenic signals during myogenesis.
Insights
Muscle protein MHox inhibits c-fos gene activation by binding to a key protein complex. This interaction blocks growth signals, preventing gene expression during muscle cell differentiation.
Area of Science:
- Molecular Biology
- Cell Signaling
- Gene Regulation
Background:
- The c-fos promoter's Serum Response Element (SRE) is crucial for growth factor signaling.
- Transcriptional activation of c-fos involves the ternary complex of Serum Response Factor (SRF) and Ternary Complex Factor (TCF).
- This promoter is typically repressed in differentiating muscle cells.
Purpose of the Study:
- To investigate the mechanism by which the c-fos promoter is repressed in differentiating muscle cells.
- To identify proteins involved in blocking mitogenic signals during myogenesis.
Main Methods:
- Investigated protein-protein interactions using co-immunoprecipitation or similar assays.
- Assessed the effect of MHox on ternary complex formation.
- Utilized reporter gene assays in fibroblasts to measure promoter activity.
Main Results:
- Discovered that the muscle homeodomain protein MHox directly interacts with Serum Response Factor accessory protein-1 (SAP-1), a TCF member.
- MHox inhibits the formation of the SRF-TCF ternary complex.
- Exogenous MHox protein suppressed serum-inducibility of an SRE-dependent reporter gene in fibroblasts.
Conclusions:
- MHox plays a role in repressing the c-fos promoter during muscle differentiation.
- MHox functions by physically inhibiting the formation of the SRF-TCF ternary complex.
- MHox is implicated in blocking mitogenic signals essential for myogenesis.