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Yeast As a Chassis for Developing Functional Assays to Study Human P53
14:57

Yeast As a Chassis for Developing Functional Assays to Study Human P53

Published on: August 4, 2019

Genotoxic exposure: novel cause of selection for a functional ΔN-p53 isoform

J P M Melis1, E M Hoogervorst, C T M van Oostrom

  • 1Laboratory for Health Protection Research, National Institute of Public Health and the Environment, Bilthoven, Utrecht, The Netherlands.

Oncogene
|December 15, 2010
PubMed

Insights

Chemicals can cause specific p53 gene mutations, leading to a truncated protein called ΔN-p53 (or p44). This isoform drives cancer development in mice and has its own transcriptional functions.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • The p53 gene is crucial for preventing cancer, with mutations frequently observed in various tumors.
  • A novel p53 mutational spectrum, distinct from typical human and murine tumor profiles, was identified.

Purpose of the Study:

  • To investigate a novel p53 mutational spectrum in 2-acetylaminofluorene (2-AAF)-induced urinary bladder tumors.
  • To elucidate the mechanism of aberrant p53 isoform (ΔN-p53 or p44) expression and its role in carcinogenesis.

Main Methods:

  • Analysis of p53 mutational spectrum in 2-AAF-induced mouse bladder tumors.
  • Investigation of downstream translation initiation and isoform expression.
  • Gene expression profiling of mouse embryonic stem (ES) cells with ΔN-p53 in a p53-null background.

Main Results:

  • A high prevalence of nonsense mutations in the N-terminus of p53 was observed, leading to ΔN-p53 expression.
  • Chemical exposure was identified as a potential selection mechanism for this truncated p53 isoform.
  • ΔN-p53 expression was linked to a cancer phenotype in mice.
  • Gene expression profiles indicated that ΔN-p53 possesses independent transcriptional functions.

Conclusions:

  • Chemicals can induce specific p53 mutations, promoting the selection and expression of the ΔN-p53 isoform.
  • The ΔN-p53 isoform plays a significant role in driving cancer development.
  • ΔN-p53 exhibits functional transcriptional properties, distinct from wild-type p53.

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