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TP63 and TP73 in cancer, an unresolved "family" puzzle of complexity, redundancy and hierarchy

Antonio Costanzo1, Natalia Pediconi2, Alessandra Narcisi1

  • 1Dermatology Unit, Department of Neuroscience, Mental Health and Sensory Organs (NESMOS), Sapienza University of Rome, Italy.

FEBS Letters
|July 2, 2014
PubMed

Insights

The p53 family, including TP63 and TP73, regulates cell functions and development. Their complex interactions and isoforms present challenges in understanding their roles in tumor suppression and oncogenesis.

Area of Science:

  • Molecular Biology
  • Genetics
  • Cell Biology

Background:

  • The TP53 gene is part of a small gene family with two paralogs: TP63 and TP73.
  • p63 and p73 proteins share structural and functional similarities with p53, acting as transcription factors regulated by post-translational modifications and cofactors.
  • p63 and p73 are crucial for embryonic development and differentiation, and also play roles in tumor suppression.

Purpose of the Study:

  • To explore the complex biology of the p53 family, including TP63 and TP73.
  • To investigate the diverse roles of p53 family members in cellular processes and disease.
  • To address the challenges posed by the complexity, redundancy, and hierarchy within the p53 signaling network.

Main Methods:

  • Review of existing literature on TP53, TP63, and TP73.
  • Analysis of post-translational modifications and cofactor interactions.
  • Examination of isoform diversity and their functional antagonism.

Main Results:

  • TP63 and TP73 genes generate multiple isoforms with opposing functions: TA-isoforms (tumor suppressors) and DN-isoforms (proto-oncogenes).
  • The p53 family acts as a network integrating developmental, metabolic, and stress signals.
  • This network controls cell metabolism, differentiation, longevity, proliferation, and cell death.

Conclusions:

  • The p53 family's intricate network governs fundamental cellular processes.
  • Understanding the complexity, redundancy, and hierarchy of the p53 family remains a significant scientific challenge.
  • Further research is needed to fully elucidate the multifaceted roles of p63 and p73 in normal development and disease states.
Keywords:
DevelopmentTP53TP63TP73Tumor suppressors

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