Related Experiment Video

Updated: Jan 16, 2026

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

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A fork in the road: PADI4 citrullinates p53 to control immune-related networks

Sayan Bhattacharjee1, Kausik Regunath1, Carol Prives1

  • 1Department of Biological Sciences, Columbia University, New York, NY, USA.

Molecular Cell
|October 3, 2025
PubMed

Insights

The tumor suppressor p53

Area of Science:

  • Molecular Biology
  • Cancer Research
  • Epigenetics

Background:

  • The p53 protein is a crucial tumor suppressor.
  • Understanding how p53 selects its transcriptional targets is key to cancer research.
  • Post-translational modifications of p53 influence its function.

Purpose of the Study:

  • To investigate the mechanism by which p53 chooses its transcriptional targets.
  • To explore the role of PADI4 in regulating p53 activity.
  • To elucidate how p53's target specificity impacts tumor suppression.

Main Methods:

  • Biochemical assays to study protein-protein interactions.
  • Chromatin immunoprecipitation to identify p53 binding sites.
  • Gene expression analysis to assess transcriptional regulation.

Main Results:

  • PADI4 citrullinates p53.
  • Citrullination redirects p53 binding from canonical sites to ETS DNA-binding sites.
  • This redirection enhances the expression of immune-related genes.
  • The process promotes tumor suppression.

Conclusions:

  • PADI4-mediated citrullination is a novel mechanism controlling p53 transcriptional specificity.
  • Altering p53's DNA-binding preference enhances anti-tumor immunity.
  • This finding offers new avenues for cancer therapy targeting p53 regulation.

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