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The role of truncated p53 isoforms in the DNA damage response

Luiza Steffens Reinhardt1, Kira Groen1, Cheryl Newton1

  • 1School of Biomedical Sciences and Pharmacy, College of Health, Medicine and Wellbeing, The University of Newcastle, Newcastle, NSW, Australia; Hunter Medical Research Institute, Newcastle, NSW, Australia.

Biochimica Et Biophysica Acta. Reviews on Cancer
|March 28, 2023
PubMed

Insights

Tumor suppressor p53 isoforms modulate DNA damage response (DDR) pathways. These isoforms can enhance or block cell death, impacting cancer chemoresistance and offering potential therapeutic targets.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Genetics

Background:

  • The tumor suppressor p53 is a key regulator of the DNA damage response (DDR).
  • p53 isoforms represent a newly discovered layer of complexity in the DDR.
  • These isoforms can modulate p53 target gene expression and protein interactions.

Purpose of the Study:

  • To review the critical role of p53 isoforms in cellular responses to DNA damage.
  • To explore the mechanisms regulating p53 isoform expression.
  • To discuss the implications of p53 isoforms in cell fate decisions and cancer.

Main Methods:

  • This review synthesizes existing literature on p53 isoforms and the DDR.
  • Focuses on mechanisms of isoform expression, including alternative splicing and translation.
  • Analyzes the functional consequences of p53 isoforms in DNA damage response pathways.

Main Results:

  • p53 isoforms are generated through alternative splicing (C-terminal) and alternative translation (N-terminal).
  • These isoforms can either enhance the canonical p53 DDR or inhibit cell death.
  • The specific effects are DNA damage and cell type-dependent.

Conclusions:

  • p53 isoforms play a significant role in determining cell fate following DNA damage.
  • Their involvement in chemoresistance highlights their importance in cancer.
  • Understanding p53 isoform function may reveal novel therapeutic strategies for cancer and other diseases.
Keywords:
Cell deathDNA damage responseDNA repairGenotoxic stressTP53

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