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Related Experiment Videos

p73 and p63: why do we still need them?

Giovanni Blandino1, Matthias Dobbelstein

  • 1Department of Experimental Oncology, Regina Elena Cancer Institute, Rome, Italy.

Cell Cycle (Georgetown, Tex.)
|July 16, 2004
PubMed
Summary

The p63 and p73 proteins, unlike p53, are crucial for development and possess distinct structures and regulatory mechanisms. Their unique roles highlight evolutionary divergence in the p53 family.

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Area of Science:

  • Molecular Biology
  • Evolutionary Biology
  • Genetics

Background:

  • p63 and p73 were initially considered homologues of p53, with unclear evolutionary significance.
  • TP63 and TP73 genes are phylogenetically older than TP53.
  • Deletion of TP63 or TP73 causes severe developmental defects, unlike TP53 deletion.

Purpose of the Study:

  • To delineate the distinct properties of p63 and p73 compared to p53.
  • To understand the evolutionary retention of p63 and p73.

Main Methods:

  • Comparative analysis of protein structure.
  • Examination of regulatory mechanisms (mRNA levels, posttranslational modifications, protein interactions).
  • Assessment of biological activities (gene expression, development, tumorigenesis).

Main Results:

  • p63 and p73 exhibit unique structural features, particularly in their transactivation and carboxyterminal domains.
  • Distinct regulatory pathways govern p63 and p73 expression and function.
  • p63 and p73 control gene expression, development, and tumorigenesis, with functions not redundant with p53.

Conclusions:

  • p63 and p73 possess unique biological roles beyond p53's functions, particularly in development.
  • Evolutionary divergence led to specialized roles, with p53 focusing on genome maintenance while p63/p73 handle broader activities.

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