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Methods for Evaluating the Role of c-Fos and Dusp1 in Oncogene Dependence
Published on: January 7, 2019
Loss of FBP function arrests cellular proliferation and extinguishes c-myc expression.
1Laboratory of Pathology, DCS, NCI, Building 10, Room 2N105, Bethesda, MD 20892-1500, USA.
The EMBO Journal
|March 4, 2000
Summary
Far upstream element-binding protein (FBP) is essential for maintaining c-myc expression. Without FBP, cellular proliferation halts, and c-myc transcription ceases, indicating FBP acts as a crucial regulator.
Area of Science:
- Molecular Biology
- Gene Regulation
- Cancer Biology
Background:
- The c-myc gene is a critical regulator of cellular proliferation.
- Multiple transcription factors bind to the c-myc regulatory region.
- Far upstream element (FUSE)-binding protein (FBP) binds to single-stranded DNA at the FUSE element.
Purpose of the Study:
- To investigate the role of FBP in regulating endogenous c-myc expression.
- To determine the mechanism by which FBP influences c-myc transcription.
- To explore the potential of FBP as a regulator of cellular proliferation.
Main Methods:
- Utilized replication-defective adenovirus vectors to express dominant-negative FBP DNA-binding domain and antisense FBP RNA.
- Assessed cellular proliferation rates.
- Measured endogenous c-myc transcription from P1 and P2 promoters.
- Analyzed the single-stranded character of the FUSE element.
Main Results:
- Absence of FBP function arrested cellular proliferation.
- Both dominant-negative FBP and antisense FBP RNA extinguished c-myc transcription.
- FBP's interaction with FUSE appears to be modulated by DNA torsional strain.
- FBP binding to FUSE correlates with promoter activity and DNA supercoiling.
Conclusions:
- FBP is indispensable for sustained endogenous c-myc expression and cellular proliferation.
- FBP acts as a sensor of torsional stress on DNA, directly measuring promoter activity.
- The FUSE element functions as a torsion-regulated switch, mediating higher-order regulation of c-myc and other factors.
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