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Detection and Visualization of DNA Damage-induced Protein Complexes in Suspension Cell Cultures Using the Proximity Ligation Assay
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Positive feedback regulation of p53 transactivity by DNA damage-induced ISG15 modification

Jong Ho Park1, Seung Wook Yang1, Jung Mi Park1

  • 1School of Biological Sciences, College of Natural Sciences, Seoul National University, Seoul 08826, Korea.

Nature Communications
|August 23, 2016
PubMed

Insights

The tumor suppressor p53

Area of Science:

  • Molecular Biology
  • Cancer Research
  • Cellular Stress Response

Background:

  • The tumor suppressor p53 is crucial for cellular defense against DNA damage.
  • ISG15 (Interferon-Stimulated Gene 15) is involved in cancer development.
  • DNA-damaging agents induce p53 and ISG15 pathway components.

Purpose of the Study:

  • To investigate the relationship between p53 and the ISG15-conjugating system under DNA damage.
  • To elucidate the role of ISG15 conjugation to p53 in regulating tumor suppression.

Main Methods:

  • Analysis of p53-responsive elements in ISG15-related genes.
  • Assessment of gene expression changes in response to DNA damage.
  • Investigation of ISG15 conjugation to p53 and its impact on p53 target gene binding.

Main Results:

  • ISG15, UBE1L, UBCH8, and EFP genes possess p53-responsive elements.
  • Their expression is induced in a p53-dependent manner following DNA damage.
  • DNA damage promotes ISG15 conjugation to p53, enhancing its binding to target gene promoters (e.g., CDKN1, BAX) and its own gene.
  • This modification involves phosphorylation and acetylation, leading to cell growth suppression.

Conclusions:

  • A novel feedback loop exists between p53 and the ISG15-conjugating system.
  • This circuit positively regulates p53's tumor-suppressive function under DNA damage.
  • ISG15 conjugation to p53 is a key mechanism for enhancing tumor suppression.

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