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

Published on: August 4, 2019

Functional regulation of p73 and p63: development and cancer

Gerry Melino1, Xin Lu, Milena Gasco

  • 1Medical Research Council, Toxicology Unit, LE1 9HN, Leicester, UK. gm89@le.ac.uk

Trends in Biochemical Sciences
|December 9, 2003
PubMed

Insights

The p53 protein family, including p53, p63, and p73, regulates cell cycles and apoptosis. Their complex regulation, involving isoforms and modifications, influences biological effects and tumor suppression.

Area of Science:

  • Molecular Biology
  • Genetics
  • Cancer Research

Background:

  • The p53 protein family, comprising p53, p63, and p73, are crucial transcription factors.
  • p63 and p73 exhibit greater molecular complexity than p53 due to alternative splicing and N-terminal deletions.
  • These proteins are involved in regulating cell cycle and apoptosis.

Purpose of the Study:

  • To explore the molecular complexity and functional regulation of the p53 protein family.
  • To understand how alternative splicing and protein modifications influence the biological effects of p53, p63, and p73.
  • To investigate the interplay between p53 family members in cellular processes and tumor suppression.

Main Methods:

  • Analysis of alternative splicing in p63 and p73 gene expression.
  • Investigation of dominant-negative protein isoforms and their regulatory mechanisms.
  • Examination of post-translational modifications impacting p53 family function.
  • Comparative analysis of knockout mouse models (p53, p63, and p73) to assess tumor susceptibility and developmental abnormalities.

Main Results:

  • p63 and p73 demonstrate significant molecular complexity through diverse C-terminal isoforms and N-terminally deleted variants.
  • Reciprocal functional regulation exists between p63 and p73 isoforms.
  • Post-translational modifications and regulatory proteins contribute to the nuanced biological activities of the p53 family.
  • Despite shared roles in cell cycle and apoptosis, p63- and p73-null mice do not exhibit increased tumor susceptibility compared to p53 knockouts.

Conclusions:

  • The p53 protein family exhibits intricate regulatory mechanisms beyond simple sequence homology.
  • Functional outcomes of p53, p63, and p73 are modulated by a combination of alternative splicing, protein variants, and post-translational modifications.
  • Complex regulatory networks fine-tune the roles of p53 family members in development and tumor suppression, suggesting context-dependent functions.

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