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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

Ribosomal protein S27L is a direct p53 target that regulates apoptosis

H He1, Y Sun

  • 1Division of Cancer Biology, Department of Radiation Oncology, University of Michigan Comprehensive Cancer Center, Ann Arbor, MI 48109-0936, USA.

Oncogene
|October 24, 2006
PubMed

Insights

The tumor suppressor p53 directly induces ribosomal protein RPS27L expression. This novel pathway promotes apoptosis, offering new insights into cancer therapy.

Area of Science:

  • Molecular Biology
  • Cancer Research
  • Cell Biology

Background:

  • Ribosomal proteins regulate p53 activity through various mechanisms.
  • Some ribosomal proteins inhibit p53 degradation, while others enhance its translation.
  • The role of ribosomal protein RPS27L in p53 regulation was previously unknown.

Purpose of the Study:

  • To investigate whether ribosomal protein RPS27L is a direct target of the tumor suppressor p53.
  • To elucidate the functional role of RPS27L in p53-mediated cellular processes, particularly apoptosis.

Main Methods:

  • Genome-wide ChIP-profiling to identify p53-inducible genes.
  • Analysis of p53-binding sites within the RPS27L gene promoter region.
  • Luciferase reporter assays to confirm p53-dependent transcriptional regulation.
  • In vitro and in vivo binding assays.
  • Apoptosis assays using gene overexpression and siRNA silencing.

Main Results:

  • RPS27L was identified as a novel p53-inducible gene.
  • A functional p53-binding site was found in the first intron of RPS27L, mediating p53-dependent transactivation.
  • p53 directly binds to the RPS27L gene promoter in vitro and in vivo.
  • Overexpression of RPS27L enhanced etoposide-induced apoptosis, while its silencing inhibited it.

Conclusions:

  • The tumor suppressor p53 directly regulates the expression of the ribosomal protein RPS27L.
  • RPS27L plays a functional role in promoting p53-mediated apoptosis.
  • This study reveals a new molecular mechanism linking p53 activity to ribosomal protein expression and apoptosis induction.

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