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Y14 governs p53 expression and modulates DNA damage sensitivity

Chia-Chen Lu1,2, Chi-Chieh Lee2, Ching-Tzu Tseng2

  • 1Taiwan International Graduate Program in Molecular Medicine, National Yang-Ming University and Academia Sinica, Taipei, Taiwan.

Scientific Reports
|April 1, 2017
PubMed

Insights

Y14 protein depletion triggers alternative p53 splicing (p53β) and DNA damage signaling. Y14 regulates p53 levels and influences cell sensitivity to genotoxic agents.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Genetics

Background:

  • Y14 is a key component of the exon junction complex (EJC) with known cellular functions.
  • Y14 depletion leads to G2/M cell cycle arrest, DNA damage, and apoptosis.
  • The role of Y14 in regulating gene expression, particularly in response to DNA damage, is under investigation.

Purpose of the Study:

  • To investigate the functional link between Y14 and p53 expression.
  • To elucidate the mechanism by which Y14 influences p53 splicing and protein levels.
  • To determine the impact of Y14 on cellular responses to genotoxic stress.

Main Methods:

  • RNA interference (RNAi) to deplete Y14 in human cells.
  • Analysis of p53 alternative splicing using RT-PCR and Western blotting.
  • Assessment of DNA damage markers and cell cycle progression.
  • Treatment with camptothecin and other genotoxic agents.

Main Results:

  • Y14 knockdown induced the expression of the p53β isoform by inhibiting aberrant exon inclusion in p53 pre-mRNA.
  • Y14, as part of the EJC, normally suppresses p53β formation.
  • Both Y14 depletion and overexpression altered total p53 protein levels, indicating a role in p53 quality control.
  • Y14 depletion reduced p21 protein levels and increased sensitivity to genotoxic agents.

Conclusions:

  • Y14 directly regulates p53 expression, including alternative splicing and protein stability.
  • Y14 functions in the DNA damage response pathway, influencing p53 signaling and cellular sensitivity to DNA-damaging drugs.
  • The findings reveal a novel role for Y14 in maintaining genomic integrity and controlling p53-mediated responses.

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