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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

p53 regulates its own activator: transcriptional co-activator PC4, a new p53-responsive gene

A Hari Kishore1, Kiran Batta, Chandrima Das

  • 1Transcription and Disease Laboratory, Molecular Biology and Genetics Unit, Jawaharlal Nehru Centre for Advanced Scientific Research, Jakkur, Bangalore-560066, India.

The Biochemical Journal
|June 9, 2007
PubMed

Insights

The tumor suppressor protein p53 induces the transcriptional co-activator PC4, which in turn enhances p53 activity. This discovery reveals a novel positive feedback loop regulating p53 function.

Area of Science:

  • Molecular Biology
  • Cancer Biology
  • Gene Regulation

Background:

  • The tumor suppressor protein p53 is a critical regulator of cellular responses, including cell cycle arrest and apoptosis.
  • Human transcriptional co-activator PC4 was previously identified as a unique activator of p53 function.

Purpose of the Study:

  • To investigate the regulatory relationship between p53 and PC4.
  • To determine if PC4 is regulated by p53 and if this interaction forms a feedback loop.

Main Methods:

  • Bioinformatics analysis to identify p53-binding sites in the PC4 promoter.
  • In vitro and in vivo experiments to confirm p53 binding to the PC4 promoter.
  • Analysis of PC4 mRNA and protein levels following p53 induction.
  • Assessment of PC4's effect on p53 recruitment to the PC4 promoter.

Main Results:

  • PC4 is identified as a p53-inducible gene with multiple p53-binding sites in its promoter.
  • p53 binds to these sites in vitro and in vivo, activating PC4 transcription.
  • PC4 mRNA and protein levels increase upon p53 induction.
  • PC4 enhances p53's recruitment to the PC4 promoter, strengthening the regulatory interaction.

Conclusions:

  • This study establishes PC4 as a p53-inducible gene.
  • A novel positive feedback loop is identified where p53 induces PC4, which then enhances p53 function.
  • This feedback loop provides a new mechanism for controlling p53 activity.

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