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

Published on: August 4, 2019

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p53 genes function to restrain mobile elements

Annika Wylie1, Amanda E Jones1, Alejandro D'Brot1

  • 1Department of Cell Biology, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA;

Genes & Development
|December 25, 2015
PubMed

Insights

The tumor suppressor p53 restricts mobile genetic elements called retrotransposons. Cancer-associated p53 mutations disable this function, suggesting p53’s role in preventing cancer involves controlling transposon activity.

Area of Science:

  • Genetics
  • Molecular Biology
  • Cancer Research

Background:

  • The p53 gene is a crucial tumor suppressor, but its precise mechanisms in cancer prevention are not fully understood.
  • p53 regulates stress responses and adaptive transcription across the animal kingdom.

Purpose of the Study:

  • To investigate the role of p53 in restricting retrotransposon activity.
  • To determine if p53's tumor suppressive function is linked to the control of mobile genetic elements.

Main Methods:

  • Utilized Drosophila and zebrafish models to study p53 function.
  • Examined genetic interactions between p53 and the piwi-interacting RNA (piRNA) pathway.
  • Analyzed retrotransposon activity in p53-deficient germlines and p53-driven cancers.
  • Performed gene complementation studies with normal and mutant human p53 alleles.

Main Results:

  • p53 was found to restrict retrotransposon activity and interact with the piRNA pathway.
  • Transposon activity increased in p53-deficient germlines, particularly after meiotic recombination.
  • Normal human p53 suppressed transposons, while cancer-derived mutant p53 alleles did not.
  • Unrestrained retrotransposons were observed in p53-driven mouse and human cancers, correlating with p53 status and chromatin marks.

Conclusions:

  • Ancestral functions of p53 involve conserved mechanisms to suppress retrotransposons.
  • The inability of mutant p53 to control transposons suggests this is a key mechanism in p53-mediated tumor suppression.
  • p53 may mitigate cancer partly by limiting transposon mobility.
Keywords:
Drosophilahuman cancersmouse cancer modelsp53piRNAsretrotransposonszebrafish

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