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Yeast As a Chassis for Developing Functional Assays to Study Human P53
14:57

Yeast As a Chassis for Developing Functional Assays to Study Human P53

Published on: August 4, 2019

Active transcription of the human FAS/CD95/TNFRSF6 gene involves the p53 family

Tobias Schilling1, Elisa Schulze Schleithoff, Astrid Kairat

  • 1Department of Internal Medicine I and Clinical Chemistry, University Hospital, 69120 Heidelberg, Germany.

Biochemical and Biophysical Research Communications
|July 21, 2009
PubMed

Insights

The p53 family, including p63 and p73, regulates the CD95 gene. Both transactivation and dominant-negative isoforms influence CD95 gene expression through promoter and intronic elements.

Area of Science:

  • Molecular Biology
  • Cancer Biology
  • Genetics

Background:

  • The p53 family, comprising p53, p63, and p73, plays critical roles in cellular processes.
  • p63 and p73 exist as transactivation (TA) and dominant-negative (DN) isoforms, influencing transcriptional activity.
  • DN isoforms can inhibit the function of TA isoforms and wild-type p53, potentially contributing to oncogenesis.

Purpose of the Study:

  • To elucidate the regulatory mechanisms of the CD95 gene by the p53 family.
  • To investigate the role of specific p53-responsive elements (REs) in the CD95 gene promoter and intron.

Main Methods:

  • Analysis of p53-responsive elements within the CD95 gene.
  • Investigating the transcriptional activation capabilities of p53 family members on the CD95 gene.

Main Results:

  • A p53-responsive element in the first intron of the CD95 gene mediated transcriptional activation by p53, TAp63, and TAp73.
  • This intronic element cooperated with three p53-REs located in the CD95 gene promoter.
  • Maximal transcriptional activation of the CD95 gene was achieved through the synergistic action of promoter and intronic p53-binding sites.

Conclusions:

  • The p53 family extensively regulates CD95 gene expression.
  • Cooperation between intronic and promoter regulatory elements is crucial for robust CD95 gene activation by p53 family members.
  • Understanding these interactions provides insights into p53 family-mediated gene regulation in cancer.

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