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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-Dependent induction of PVT1 and miR-1204

Anthony M Barsotti1, Rachel Beckerman, Oleg Laptenko

  • 1Department of Biological Sciences, Columbia University, New York, New York 10027, USA.

The Journal of Biological Chemistry
|November 24, 2011
PubMed

Insights

The tumor suppressor protein p53 directly regulates the PVT1 locus, inducing miR-1204. This microRNA then increases p53 levels, promoting cell death in cancer research.

Area of Science:

  • Molecular Biology
  • Genetics
  • Cancer Research

Background:

  • The tumor suppressor protein p53 is a transcription factor regulating gene expression.
  • p53's role in regulating non-coding RNAs, including microRNAs and long non-coding RNAs, is an emerging area of research.
  • The PVT1 locus is a large, complex non-coding RNA-producing region implicated in cancer.

Purpose of the Study:

  • To investigate whether the PVT1 locus is a direct target of p53 transcriptional regulation.
  • To determine if p53 regulates any of the microRNAs encoded within the PVT1 locus.
  • To explore the functional consequences of PVT1-derived microRNA regulation by p53.

Main Methods:

  • Chromatin immunoprecipitation (ChIP) to identify p53 binding sites.
  • Electrophoretic mobility shift assay (EMSA) to confirm p53-DNA interaction.
  • Luciferase reporter assays to assess transcriptional activation.
  • Quantitative analysis of endogenous PVT1 transcripts and mature miR-1204 levels.
  • Functional assays involving ectopic miR-1204 expression.

Main Results:

  • p53 directly binds to and activates a response element near miR-1204 within the PVT1 locus.
  • p53-dependent induction of PVT1 transcripts and subsequent upregulation of mature miR-1204 were observed.
  • Ectopic expression of miR-1204 resulted in elevated p53 levels.
  • miR-1204 overexpression induced cell death in a manner partially dependent on p53.

Conclusions:

  • The PVT1 locus is a novel p53 target gene, with p53 directly regulating miR-1204 transcription.
  • A feedback loop exists where p53 induces miR-1204, which in turn enhances p53 levels and promotes cell death.
  • These findings reveal a new regulatory axis involving p53, PVT1, and miR-1204 with implications for cancer biology.

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