p53 Homologue p63 represses epidermal growth factor receptor expression

Area of Science:

• Molecular Biology
• Cancer Biology
• Gene Regulation

Background:

• Tumor suppressor p53 transactivates epidermal growth factor receptor (EGFR) expression.
• p63 gene products are p53 relatives with similar functions.
• The role of TAp63gamma in EGFR regulation was previously unknown.

Purpose of the Study:

• To investigate the function of TAp63gamma in regulating EGFR expression.
• To elucidate the mechanism by which TAp63gamma affects EGFR promoter activity.

Main Methods:

• Transient transfection assays to assess EGFR promoter activity.
• Electrophoretic mobility shift assays (EMSA) to study DNA-protein interactions.
• Immunoprecipitation to analyze protein interactions.

Main Results:

• TAp63gamma showed minimal binding to the EGFR promoter's p53-responsive element.
• TAp63gamma repressed basal EGFR promoter activity and endogenous EGFR expression.
• Repression was dependent on Sp1 binding sites in the EGFR promoter (-348 to -293).
• TAp63gamma directly interacted with Sp1, impairing Sp1 binding to DNA.

Conclusions:

• TAp63gamma negatively regulates EGFR gene expression.
• This regulation occurs through TAp63gamma's interaction with the transcription factor Sp1.
• TAp63gamma's interaction with basal transcription factors provides a novel mechanism for EGFR gene regulation.