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Updated: Nov 8, 2025

Detection and Visualization of DNA Damage-induced Protein Complexes in Suspension Cell Cultures Using the Proximity Ligation Assay
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Ring finger 20/ring finger 40/WW domain-containing adaptor with coiled-coil complex interacts with p53 to regulate

Danni Meng1, Kun Guo1, Die Zhang1

  • 1College of Life Sciences, Shanghai Normal University, Shanghai 200234, P.R. China.

Oncology Letters
|April 19, 2021
PubMed

Insights

The RNF20/RNF40/WAC complex directly binds to the p53 DNA-binding domain at site R282, crucial for regulating gene transcription in DNA damage response. This interaction is vital for maintaining p53 tumor suppressor function.

Area of Science:

  • Molecular Biology
  • Cancer Research
  • Epigenetics

Background:

  • p53 is a critical tumor suppressor gene regulating cell cycle arrest and DNA repair.
  • The RNF20/RNF40/WAC complex, a histone H2B ubiquitination E3 ligase, is implicated in oncogenesis.
  • Histone H2B mono-ubiquitination is essential for p53 functionality.

Purpose of the Study:

  • To identify specific binding sites of the RNF20/RNF40/WAC complex within the p53 DNA-binding domain.
  • To elucidate the role of this interaction in gene regulation during DNA damage response.

Main Methods:

  • Investigated the interaction between p53 and the RNF20/RNF40/WAC complex.
  • Mapped the interaction to coiled-coil regions of RNF20, RNF40, and WAC, and the R282 site in p53's DNA-binding domain.
  • Utilized RNF20/RNF40 knockout and R282W p53 mutation models in HCT116 cells.

Main Results:

  • p53 directly interacts with the RNF20/RNF40/WAC complex via its coiled-coil regions.
  • The R282 site in p53's DNA-binding domain is a key binding site for the complex.
  • RNF20/RNF40 knockout and the R282W mutation in p53 reduced p53 and target gene expression, impairing DNA damage response.

Conclusions:

  • The RNF20/RNF40/WAC complex interacts with p53 at the R282 site, modulating its transcriptional activity.
  • This interaction is crucial for regulating gene transcription in response to DNA damage.
  • Defects in this complex or p53 mutations disrupt tumor suppressor functions.
Keywords:
coiled-coil domaingene transcriptionp53p53 missense mutation R282Wring finger 20/ring finger 40/WW domain-containing adaptor with coiled-coil complex

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